MIEMCAL 


Gift  of 
Robert  S.  Stone,  M.D. 


TEXT-BOOK  OF 


EMBRYOLOGY 


BY 


FREDERICK  RANDOLPH  BAILEY,  A.  M.,  M.  D. 

FORMERLY   ADJUNCT  PROFESSOR   OF   HISTOLOGY   AND   EMBRYOLOGY,   COLLEGE   OF  PHYSICIANS  AND 

SURGEONS  (MEDICAL  DEPARTMENT  OF  COLUMBIA  UNIVERSITY) 


AXD 


ADAM  MARION  MILLER,  A.  M. 

PROFESSOR   OF   ANATOMY,   LONG  ISLAND   COLLEGE   HOSPITAL 
AND   AFFILIATED   INSTITUTIONS 


WITH 
FIVE  HUNDRED  AND  FIFTEEN  ILLUSTRATIONS 


NEW  YORK 

WILLIAM  WOOD  AND  COMPAJSTY 
MDCCCCXVIII 


COPYRIGHT,  1916, 
BY  WILLIAM  WOOD  &  COMPANY. 


PREFACE  TO  THE  THIRD  EDITION 


In  the  present  edition  the  general  plan  of  the  book,  as  outlined  in  the 
preface  to  the  first  edition,  remains  unchanged  with  the  exception  that 
Practical  Suggestions  at  the  end  of  each  chapter  and  the  Appendix  dealing 
with  general  technic  are  omitted.  Certain  changes  have  been  made  in  the 
text  and  illustrations.  Several  chapters  have  been  rewritten  in  the  light  of 
recent  studies,  numerous  changes  have  been  made  throughout  the  book  in 
view  of  the  advances  made  in  the  science,  and  a  number  of  new  illustrations 
supplant  the  old. 

The  writers  wish  to  thank  Mr.  Adolph  Elwyn  for  the  revision  of  the. 
chapters  on  Maturation  and  Fertilization. 

THE  AUTHORS. 
JULY  24,  1916. 


iii 


81530 


PREFACE  TO  THE  FIRST  EDITION 


The  Text-book,  as  originally  planned,  is  an  outgrowth  of  the  course  in 
Embryology  given  at  the  Medical  Department  of  Columbia  University.  It  was 
intended  primarily  to  present  to  the  student  of  medicine  the  most  important 
facts  of  development,  at  the  same  time  emphasizing  those  features  which 
bear  directly  upon  other  branches  of  medicine.  As  the  work  took  form,  it 
seemed  best  to  broaden  its  scope  and  make  it  of  greater  value  to  the  general 
student  of  embryology  and  allied  sciences.  With  the  opinion  that  illustrations 
convey  a  much  clearer  conception  of  structural  features  than  verbal  description, 
alone,  the  writers  have  made  free  use  of  figures. 

The  plan  of  adding  brief  "Practical  Suggestions"  at  the  end  of  each  chapter 
has  been  so  thoroughly  satisfactory  in  the  Text-book  of  Histology,  especially 
in  connection  with  laboratory  work,  that  it  has  been  adopted  here.  These 
"suggestions"  are  not  intended  to  be  complete  descriptions  of  embryological 
technic,  but  are  for  the  purpose  of  furnishing  the  laboratory  worker  with  cer- 
tain of  the  more  essential  practical  hints  for  studying  the  structures  described 
in  the  chapter.  To  avoid  frequent  repetition,  some  of  the  best  methods  of 
procuring,  handling,  and  preparing  embryological  material,  and  some  of  the 
more  important  formulae  are  given  in  the  Appendix,  which  is  intended  to  be 
used  mainly  for  the  carrying  out  of  the  "Practical  Suggestions." 

The  development  of  the  Germ  Layers  has  been  treated  rather  elaborately 
from  a  comparative  standpoint,  because  this  has  been  found  the  most  satisfac- 
tory method  of  teaching  the  subject. 

In  the  chapter  on  the  Nervous  System  the  aim  has  been  to  give  a  general 
conception  of  the  subject,  which,  if  once  mastered  by  the  student,  will  give 
him  an  insight  into  the  structure  and  significance  of  the  nervous  system  that 
will  bring  this  difficult  subject  more  fully  within  his  grasp. 

In  Part  II  (Organogenesis) ,  at  the  end  of  each  chapter  there  is  given  a  brief 
description  of  certain  developmental  anomalies  which  may  occur  in  connection 


VI 


PREFACE. 


with  the  organs  described  in  the  chapter.  In  Chapter  XIX  (Teratogenesis) 
the  nature  and  origin  of  the  more  complex  anomalies  and  monsters  are  dis- 
cussed, and  also  the  causes  underlying  the  origin  of  malformations. 

The  writers  wish  to  thank  Dr.  Oliver  S.  Strong  for  his  painstaking  work  on 
the  chapter  on  the  Nervous  System.  Dr.  Strong  in  turn  wishes  to  acknowledge 
his  indebtedness  to  Dr.  Adolf  Meyer  for  important  ideas  underlying  the  treat- 
ment of  his  subject,  and  also  for  many  valuable  details.  He  expresses  his 
thanks  also  to  Professors  C.  J.  Herrick,  H.  von  W.  Schulte  and  G.  L.  Streeter 
for  helpful  criticisms  and  suggestions.  The  writers  would  also  express  their 
thanks  to  Dr.  H.  McE.  Knower  for  helpful  criticisms  on  Part  I  and  the 
chapter  on  Teratogenesis;  to  Dr.  Edward  Learning  for  making  the  photo- 
graphs reproduced  in  the  text;  to  the  American  Journal  of  Anatomy  for  the 
loan  of  plates;  and  to  Messrs.  William  Wood  &  Company  for  their  uniform 
courtesy  and  kindness. 

FREDERICK  RANDOLPH  BAILEY. 
APRIL  i,  1909.  ADAM  MARION  MILLER. 


CONTENTS 


PART  I.-GENERAL  DEVELOPMENT 

CHAPTER  I 

THE  CELL  AND  CELL  PROLIFERATION i 

The  Cell .  i 

Cell  Division 3 

Amitosis .  3 

Mitosis 4 

References  for  Further  Study 9 

CHAPTER  II 

THE  GERM  CELLS — OVTJM  AND  SPERMATOZOON 10 

The  Ovum i  o 

The  Spermatozoon 13 

References  for  Further  Study 15 

CHAPTER  III 

MATURATION 17 

Spermatogenesis — Maturation  of  the  Sperm 17 

Maturation  of  the  Ovum 21 

Significance  of  Mitosis  and  Maturation 25 

Sex  Determination 27 

Ovulation  and  Menstruation 29 

References  for  Further  Study 32 

CHAPTER  IV 

FERTILIZATION 33 

Significance  of  Fertilization 38 

References  for  Further  Study 39 

CHAPTER  V 

CLEAVAGE  (SEGMENTATION) 40 

Forms  of  Cleavage 40 

Holoblastic  Cleavage 41 

Equal 41 

Unequal 42 

vii 


Viii  CONTENTS 

Meroblastic  Cleavage 44 

Superficial 44 

Discoidal 45 

References  for  Further  Study 50 

CHAPTER  VI 

GERM  LAYERS 51 

The  Two  Primary  Germ  Layers — Formation  of  the  Gastrula 51 

Gastrulation  in  Amphioxus 51 

Gastrulation  in  Amphibians 52 

Gastrulation  in  Reptiles  and  Birds 57 

Gastrulation  in  Mammals 63 

Formation  of  the  Middle  Germ  Layer — Mesoderm 68 

Mesoderm  Formation  in  Amphioxus 68 

Mesoderm  Formation  in  Amphibians 72 

Mesoderm  Formation  in  Reptiles  and  Birds 74 

Mesoderm  Formation  in  Mammals 81 

The  Germ  Layers  in  Man .  85 

References  for  Further  Study 92 

CHAPTER  VII 

FCETAL  MEMBRANES 95 

Foetal  Membranes  in  Birds  and  Reptiles 95 

The  Amnion 95 

The  Yolk  Sac 99 

The  Allantois  . 102 

The  Chorion  or  Serosa 103 

Foetal  Membranes  in  Mammals 103 

Amnion,  Chorion,  Yolk  Sac,  Allantois,  Umbilical  Cord 104 

Further  Development  of  the  Chorion. 107 

The  Fcetal  Membranes  in  Man in 

The  Amnion m 

The  Yolk  Sac 113 

The  Allantois 114 

The  Chorion  and  Decidua 115 

The  Decidua  Parietalis 119 

The  Decidua  Capsularis 119 

The  Decidua  Basalis 120 

The  Umbilical  Cord 128 

The  Expulsion  of  the  Placenta  and  Membranes 130 

Anomalies !3o 

References  for  Further  Study 131 


CONTENTS  ix 

CHAPTER  VIII 

THE  DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY 133 

Branchial  Arches — Face — Neck 145 

The  Extremities 149 

Age  and  Length  of  Embryos 151 

Normal,  Abnormal  and  Pathological  Embryos 154 

References  for  Further  Study 155 

PART  II.-ORGANOGENESIS 

CHAPTER  IX 

THE  DEVELOPMENT  OF  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM  .    .  161 

Histogenesis 163 

Fibers  and  Fibrils 166 

Adipose  Tissue 167 

Cartilage 168 

Osseous  Tissue 169 

Intramembranous  Ossification 169 

Intracartilaginous  Ossification ' 172 

The  Development  of  the  Skeletal  System 178 

The  Axial  Skeleton 178 

The  Notochord 178 

The  Vertebrae 179 

The  Ribs 184 

The  Sternum 185 

The  Head  Skeleton 186 

Ossification  of  the  Chondrocranium 190 

Membrane  Bones  of  the  Skull 192 

Bones  Derived  from  the  Branchial  Arches 194 

The  Appendicular  Skeleton 198 

Development  of  Joints 205 

Anomalies 209 

References  for  Further  Study 213 

CHAPTER  X 

THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 216 

The  Blood  Vascular  System 216 

Principles  of  Vasculogenesis 224 

The  Heart 227 

The  Septa 233 

The  Valves 236 

Changes  after  Birth 237 

The  Arteries 240 

The  Veins 250 


X  CONTENTS 

Histogenesis  of  the  Blood  Cells.    .    .    .' 267 

The  Lymph  Vascular  System 273 

The  Lymph  Glands 280 

The  Spleen 283 

Glomus  Coccygeum 285 

Anomalies 285 

References  for  Further  Study 290 

CHAPTER  XI 

THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM 293 

The  Skeletal  Musculature 293 

Muscles  of  the  Trunk 295 

Muscles  of  the  Head 300 

Muscles  of  the  Extremities 303 

Histogenesis  of  Striated  Voluntary  Muscle  Tissue 307 

The  Visceral  Musculature 311 

Histogenesis  of  Heart  Muscle 311 

Histogenesis  of  Smooth  Muscle 312 

Anomalies 313 

References  for  Further  Study 314 

CHAPTER  XII 

THE  DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS   .    .311 

The  Mouth 317 

The  Tongue 320 

The  Teeth 322 

The  Salivary  Glands 327 

The  Pharynx 329 

The  Branchial  Epithelial  Bodies 331 

The  (Esophagus  and  Stomach 335 

The  Intestine 337 

Histogenesis  of  the  Gastrointestinal  Tract 342 

The  Development  of  the  Liver 345 

Histogenesis  of  the  Liver 349 

The  Development  of  the  Pancreas 350 

Histogenesis  of  the  Pancreas 353 

Anomalies 354 

References  for  Further  Study 358 

CHAPTER  XIII 

THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM 360 

The  Larynx 361 

The  Trachea 363 


CONTENTS  XI 

The  Lungs 364 

Changes  in  the  Lungs  at  Birth . 367 

Anomalies 368 

References  for  Further  Study 369 

CHAPTER  XIV 

THE  DEVELOPMENT  OF  THE  CCELOM,  THE  PERICARDIUM,  PLEUROPERITONEUM, 

DIAPHRAGM  AND  MESENTERIES 370 

The  Pericardial  Cavity,  Pleural  Cavities  and  Diaphragm 371 

The  Pericardium  and  Pleura 378 

The  Omentum  and  Mesentery 378 

The  Greater  Omentum  and  Omental  Bursa 378 

The  Lesser  Omentum 379 

The  Mesenteries 380 

The  Peritoneum 382 

Anomalies 382 

References  for  Further  Study 383 

CHAPTER  XV 

THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM 384 

The  Pronephros 384 

The  Mesonephros 386 

The  Kidney  (Metanephros) 391 

The  Ureter,  Renal  Pelvis,  and  Straight  Renal  Tubules 391 

The  Convoluted  Renal  Tubules  and  Glomeruli 393 

The  Renal  Pyramids  and  Renal  Columns 397 

Changes  in  the  Position  of  the  Kidneys 399 

The  Urinary  Bladder,  Urethra,  and  Urogenital  Sinus 400 

The  Genital  Glands 403 

The  Germinal  Epithelium  and  Genital  Ridge 403 

Differentiation  of  the  Genital  Glands 405 

The  Ovary 406 

The  Testicle 411 

Determination  of  Sex 412 

The  Ducts  of  the  Genital  Glands  and  the  Atrophy  of  the  Meso- 

nephroi 413 

In  the  Female 413 

Oviduct 414 

Uterus  and  Vagina 415 

In  the  Male 416 

Changes  hi  the  Positions  of  the  Genital  Glands  and  the  Development 

of  their  Ligaments 417 

Descent  of  the  Testicles 419 

Descent  of  the  Ovaries 422 


Xll  CONTENTS 

The  External  Genital  Organs 423 

The  Development  of  the  Suprarenal  Glands 426 

The  Cortical  Substance 427 

The  Medullary  Substance 427 

Anomalies 429 

References  for  Further  Study 435 

CHAPTER  XVI 

THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM 437 

The  Skin 437 

The  Nails 439 

The  Hair ,, 440 

The  Glands  of  the  Skin 442 

The  Mammary  Glands 442 

Anomalies 444 

References  for  Further  Study 446 

CHAPTER  XVII 

THE  NERVOUS  SYSTEM 447 

General  Considerations 447 

General  Plan  of  the  Vertebrate  Nervous  System 450 

Spinal  Cord  and  Nerves 457 

The  Epichordal  Segmental  Brain  and  Nerves 459 

The  Cerebellum 466 

The  Mid-Brain  Roof 467 

The  Prosencephalon 467 

General  Development  of  the  Human  Nervous  System  During  the  First 

Month 472 

Histogenesis  of  the  Nervous  System 478 

Epithelial  Stage — Cell  Proliferation 479 

Early  Differentiation  of  the  Nerve  Elements 483 

Differentiation  of  the  Peripheral  Neurones  of  the  Cord  andj  Epi- 
chordal Segmental  Brain 486 

Efferent  Peripheral  Neurones 486 

Afferent  Peripheral  and  Sympathetic  Neurones 489 

Development  of  the  Lower  (Intersegmental)  Intermediate  Neurones.  502 

Further  Differentiation  of  the  Neural  Tube  .    .    .    .    .    .    . 506 

The  Spinal  Cord 506 

The  Epichordal  Segmental  Brain ..512 

The  Cerebellum 525 

Corpora  Quadrigemina 530 

The  Diencephalon 53! 


CONTENTS  Xlll 

The  Telencephalon  (Rhinencephalon,  Corpora  Striata  and  Pallium) .  538 

Rhinencephalon 540 

Corpora  Striata  and  Pallium 541 

The  Archipallium 546 

The  Neopallium 552 

Anomalies 560 

References  for  Further  Study 561 

CHAPTER  XVIII 

THE  ORGANS  OF  SPECIAL  SENSE 563 

The  Eye 563 

The  Lens 565 

The  Optic  Cup 569 

The  Retina 570 

The  Chorioid  and  Sclera 575 

The  Vitreous 575 

The  Optic  Nerve 576 

The  Ciliary  Body,  Iris,  Cornea,  Anterior  Chamber 577 

The  Eyelids 578 

The  Nose .  579 

The  Ear 582 

The  Inner  Ear 582 

The  Acoustic  Nerve 588 

The  Middle  Ear 589 

The  Outer  Ear 590 

Anomalies 591 

References  for  Further  Study 592 

CHAPTER  XIX 

TERATOGENESIS 593 

Malformations  Involving  More  Than  One  Individual 593 

Classification,  Description,  Origin 593 

Symmetrical  Duplicity 594 

Origin  of  Symmetrical  Duplicity 599 

Asymmetrical  Duplicity 600 

Origin  of  Asymmetrical  (Parasitic)  Duplicity 602 

Malformations  Involving  One  Individual 604 

Description,  Origin 604 

Defects  in  the  Region  of  Neural  tube 604 

Origin  of  Malformations  in  the  Region  of  Neural  Tube  ....  607 

Defects  in  Regions  of  the  Face  and  Neck,  and  their  Origin   .    .  608 

Defects  in  the  Thoracic  and  Abdominal  Regions,  and  their  Origin  610 


XIV  CONTENTS 

Causes  Underlying  the  Origin  of  Monsters 612 

The  Production  of  Duplicate  (Polysomatous)  Monsters 613 

The  Production  of  Monsters  in  Single  Embryos 614 

The  Significance  of  the  Foregoing  in  Explaining  the  Production  of 

Human  Monsters 615 

References  for  Further  Study 615 


INTRODUCTION 


While  Embryology  as  a  science  is  of  comparatively  recent  date,  recorded 
observations  upon  the  development  of  the  foetus  date  back  as  far  as  1600  when 
Fabricius  ab  Aquapendente  published  an  article  entitled  "De  Formato  Fcetu." 
Four  years  later  the  same  author  added  some  further  observations  under  the 
title,  "  De  Formatione  Foetus.'1  Harvey  (1651),  using  a  simple  lens,  studied  and 
described  the  chick  embryo  of  two  days'  incubation.  Harvey's  idea  was  that 
the  ovum  consisted  of  fluid  in  which  the  embryo  appeared  by  spontaneous 
generation.  Regnier  de  Graaf  (1677)  described  the  ovarian  follicle  (Graafian 
follicle),  and  in  the  same  year  was  announced  the  discovery  by  Von  Loewenhoek 
of  the  spermatozoon.  These  and  other  embryologists  of  this  period  held  what 
is  now  known  as  the  prejormation  theory.  According  to  this  theory,  the  adult 
form  exists  in  miniature  in  the  egg  or  germ,  development  being  merely  an 
enlarging  and  unfolding  of  preformed  parts.  With  the  discovery  of  the 
spermatozoon  the  "  pref ormationists "  were  divided  into  two  schools,  one  hold- 
ing that  the  ovum  was  the  container  of  the  miniature  individual  (ovists),  the 
other  according  this  function  to  the  spermatozoon  (animalculists).  According 
to  the  ovists,  the  ovum  needed  merely  the  stimulation  of  the  spermatozoon  to 
cause  its  contained  individual  to  undergo  development,  whereas  the  animalcu- 
lists looked  upon  the  spermatozoon  as  the  essential  embryo-container,  the  ovum 
serving  merely  as  a  suitable  food-supply  or  growing-place. 

Nearly  a  hundred  years  of  almost  no  further  progress  in  embryological 
knowledge  came  to  a  close  with  the  publication  of  Wolff's  important  article, 
"Theoria  Generationis,"  in  1759.  Wolff's  theory  was  theory  pure  and  simple, 
with  very  little  basis  on  then  known  facts,  but  it  was  significant  as  being  ap- 
parently the  first  clear  statement  of  the  doctrine  of  epigenesis.  The  two  es- 
sential points  in  Wolff's  theory  were:  (i)  that  the  embryo  was  not  preformed; 
that  is,  did  not  exist  in  miniature  in  the  germ,  but  developed  from  a  more  or  less 
unformed  germ  substance;  (2)  that  union  of  male  and  female  substances  was 
necessary  to  initiate  development.  The  details  of  Wolff's  theory  were  wrong 
in  that  he  looked  upon  the  ovum  as  a  structureless  substance  and  upon  the 
seminal  fluid  and  not  upon  the  spermatozoon  as  the  male  fecundative  agent. 
Dollinger  and  his  two  pupils,  von  Baer  and  Pander,  were  the  next  to  make 
important  contributions  to  Embryology.  Von  Baer's  publication  in  1829  was 
of  extreme  significance  in  the  development  of  embryological  knowledge,  for 

XV 


xvi  INTRODUCTION. 

in  it  we  have  the  first  definite  description  of  the  primary  germ  layers  as  well  as 
the  first  accurate  differentiation  between  the  Graafian  follicle  and  the  ovum. 
It  will  be  remembered  that  the  cell  was  not  as  yet  recognized  as  the  unit  of 
organic  structure.  Only  comparatively  gross  Embryology  was  thus  possible. 
With  the  recognition  of  the  cell  as  the  basis  of  animal  structure  (Schleiden  and 
Schwann,  1839)  the  entire  field  of  histogenesis  was  opened  to  the  embryologist; 
the  ovum  became  known  as  a  typical  cell,  while  a  little  later  (Kolliker,  Reichert 
and  others,  about  1840)  was  established  the  function  of  the  spermatozoon 
and  the  fact  that  it  also  was  a  modified  cell  structure.  From  this  time  we 
may  consider  the  two  fundamental  facts  of  Histology  and  of  Embryology, 
respectively,  as  firmly  fixed  beyond  controversy;  for  Histology,  the  fact  that 
the  body  consists  wholly  of  cells  and  cell  derivatives;  for  Embryology,  the 
fact  that  all  of  these  cells  and  cell  derivatives  develop  from  a  single  original 
cell^the  fertilized  ovum. 

The  adult  body  being  thus  composed  of  an  enormous  number  of  cells,  vary- 
ing in  structure  and  in  function,  forming  the  different  tissues  and  organs,  and 
these  cells  having  all  developed  from  the  single  fertilized  germ  cell,  it  is  the 
province  of  Embryology  to  trace  this  development  from  the  union  of  male 
and  female  germ  cells  to  the  cessation  of  developmental  life. 

While  Embryology  thus  properly  begins  with  the  fertilized  ovum,  that  is, 
with  the  first  cell  of  the  new  individual,  certain  preliminary  considerations  are 
essential  to  the  proper  understanding  of  this  cell  and  its  future  development. 
These  are  the  structure  of  the  ovum  and  of  the  spermatozoon  and  their  de- 
velopment preparatory  to  union.  Also,  as  it  is  with  cells  and  cell  activities 
that  Embryology  has  largely  to  deal,  it  is  necessary  to  consider  the  structure 
of  the  typical  animal  cell  and  the  processes  by  which  cells  undergo  division  or 
proliferation. 

While  the  subject  of  this  work  is  distinctly  human  Embryology,  it  is  neither 
possible  nor  advisable  to  confine  our  study  wholly  to  human  material.  It  is  not 
possible,  for  the  reason  that  material  for  the  study  of  the  earliest  stages  in  the 
human  embryo  (first  12  days)  is  entirely  wanting,  while  human  embryos  of 
under  20  days  are  extremely  rare.  Again,  even  later  stages  in  human  develop- 
ment are  often  best  understood  by  comparison  with  similar  stages  in  lower 
forms.  For  practical  study  by  the  student,  human  material  for  all  even  of 
the  later  stages  is  rarely  available,  so  that  recourse  must  frequently  be  had  to 
material  from  lower  animals.  Such  study  is,  however,  usually  thoroughly 
satisfactory  if  the  student  has  sufficient  knowledge  of  comparative  anatomy,  and 
the  deductions  regarding  human  development,  from  the  study  of  development 
in  lower  forms,  are  rarely  in  error ~ 


PART  I. 


GENERAL  DEVELOPMENT. 


A  TEXT-BOOK  OF  EMBRYOLOGY 


CHAPTER  I. 

THE  CELL  AND  CELL  PROLIFERATION. 
THE  CELL. 

The  Typical  Animal  Cell  (Fig.  i)  is  a  small  definitely  restricted  mass  of 
protoplasm.  It  contains  or  has  at  some  period  of  its  development  contained 
two  specially  differentiated  bodies,  the  nucleus  and  the  centrosome.  It  may  be 
limited  by  a  more  or  less  definite  cell  membrane. 

Of  the  ultimate  structure  of  living  protoplasm  our  knowledge  is  extremely 
small.  It  is  of  an  albuminous  nature,  coagulated  by  heat  and  by  many  chemical 
reagents.  It  varies  both  in  structure  and  in  chemical  composition  in  different 
cells  and  is  probably  best  considered,  not  as  a  definite  structure  either  chemically 
or  morphologically,  but  as  the  material  basis  of  life  activities.  Protoplasm  can 
usually  be  resolved  into  a  formed  part,  spongioplasm,  which  takes  the  form  of  a 
reticulum,  a  feltwork,  or  fibrillae,  and  an  unformed  homogeneous  element, 
hyaloplasm,  which  fills  in  the  meshes  of  the  reticulum  or  forms  the  perifibrillar 
substance.  Various  protoplasmic  inclusions  are  frequently  found  in  cells.  To 
these  the  term  metaplasm  (paraplasm,  deutoplasm)  has  been  applied.  Among 
them  may  be  mentioned  plastids,  fat  droplets,  pigment  granules  and  various 
excretory  and  secretory  substances. 

The  NUCLEUS  is  usually  separated  from  the  rest  of  the  protoplasm  by  a 
nuclear  membrane.  Within  the  nucleus  the  nuclear  membrane  is  continuous 
with  a  nuclear  reticulum  which  consists  of  two  parts:  a  chromatic  part — chroma- 
tin,  and  an  achromatic  part — linin.  At  nodal  points  of  the  network  there  are 
frequently  considerable  accumulations  of  chromatin  to-  form  net  knots  (false 
nucleoli  or  karyosomes).  Filling  the  meshes  of  the  nuclear  reticulum  is  a  fluid 
or  semifluid  substance,  the  nucleoplasm  or  karyoplasm.  The  structure  of  the 
nucleus  is  thus  seen  to  correspond  closely  to  the  structure  of  the  surrounding 
protoplasm.  This  is  especially  evident  in  those  cells  in  which  there  is  no 
limiting  nuclear  membrane,  the  nuclear  reticulum  and  the  cytoreticulum  being 
ccntinuous,  the  nucleoplasm  and  cytoplasm  mingling.  This  condition,  true 


TEXT-BOOK  OF  EMBRYOLOGY. 


only  for  some  resting  cells,  is  always  present  in  cells  which  are  undergoing 
mitotic  division. 

In  addition  to  the  net  knots  are  the  truenucleoli or  plasmosomes.  These  are 
spheroidal  bodies  which  lie  free  in  the  meshes  of  the  nuclear  reticulum.  They 
vary  in  number  in  different  cells  and  sometimes  in  the  same  cell  in  different 
conditions  of  activity.  They  stain  intensely  with  basic  dyes.  The  function 
of  the  nucleolus  is  not  known.  It  has  been  regarded  by  some  as  material  in 
process  of  constructive  metabolism,  by  others  as  a  waste  product. 

The  nucleus  is  typically  spherical.  Its  shape  may  or  may  not  be  modified 
by  the  shape  of  the  cell  body.  Nuclei  may  assume  very  irregular  shapes,  as  in 
polymorphonuclear  leucocytes,  or  they  may  be  lobulated,  as  in  some  of  the 


Cell  membrane  " 


Metaplasm  1 
granules    J 

Karyosome  or  ) 
net  knot       j 


Hyaloplasm 
Spongioplasm 

Linin  network 
Nucleoplasm 


Aster  (attraction-sphere) 
Centriole 


","'    Plastids  (metaplasm) 


Chromatin  network 
Nuclear  membrane 

Nucleolus 


Vacuole 


FIG.  i. — Diagram  of  a  typical  cell.     Bailey. 

large  cells  of  bone  marrow;  or  a  cell  may  have  a  number  of  nuclei.  The  shape 
of  the  nucleus  may  vary  considerably  within  comparatively  short  periods  of  time. 
Such  nuclei  have  been  described  as  having  amceboid  movement.  The  size 
of  the  nucleus  also  appears  to  be  independent  of  the  size  of  the  cell  body,  some 
large  cells  having  small  nuclei,  while  some  small  cells  are  almost  completely 
filled  by  their  nuclei.  The  nucleus  tends  to  lie  near  the  center  of  the  cell,  yet 
may  be  eccentric  to  any  degree  and  appears  to  be  suspended  in  the  cytoplasm 
in  such  a  way  that  its  location  within  the  cell  may  change.  In  some  of  the  lowest 
forms  no  true  nuclear  structure  exists,  scattered  granules  of  chromatin  consti- 
tuting the  rudimentary  nucleus,  generally  called  a  diffuse  nucleus. 

As  the  nucleus  is  an  essential  element  in  all  reproduction,  it  follows  that  all 
cells  have  been  nucleated  at  some  time  in  their  developmental  history,  and  that 
the  adult  nonnucleated  condition  of  some  cells  (e.g.,  respiratory  epithelium) 
is  indicative  of  their  having  passed  beyond  the  age  of  reproductive  power.  If 
the  nucleus  be  removed  from  a  living  cell,  the  cytoplasm  does  not  necessarily 


THE   CELL  AND   CELL  PROLIFERATION.  3 

die,  but  may  live  for  some  time  and  show  active  motile  powers.  Such  a  de- 
nucleated  cell  has,  however,  lost  two  of  its  most  important  functions:  (i)  its 
power  of  constructive  metabolism;  that  is,  of  taking  up  nutritive  material  from 
without  and  building  this  up  into  its  own  peculiar  structure — the  power  of 
repair;  and  (2)  the  power  of  reproduction.  For  these  reasons  the  nucleus  has 
been  considered  as  especially  presiding  over  these  two  cell  functions. 

The  CEXTROSOME  is  a  structure  found  in  the  cytoplasm  near  the  nucleus, 
less  commonly  within  the  nucleus.  It  consists  typically  of  a  minute  central 
granule,  the  centriole,  a  relatively  clear  surrounding  area,  the  centrosphere,  and, 
radiating  from  this,  the  delicate  rays  which  constitute  the  aster  or  attraction 
sphere  (Fig.  i).  On  account  of  the  behavior  of  the  centrosome  in  relation  to 
cell  division,  it  is  usually  looked  upon  as  the  dynamic  center  of  the  cell. 

In  the  simplest  forms  of  animal  life  a  single  cell,  such  as  has  been  described 
above,  constitutes  the  entire  individual,  and  as  such  is  capable  of  performing 
the  functions  which  are  recognized  as  characteristic  of  living  organisms — metab- 
olism, irritability,  motion,  reproduction  and  special  functions.  The  develop- 
mental history  of  such  an  individual  is  extremely  simple.  The  nucleus  under- 
goes division  and  this  is  accompanied  or  followed  by  division  of  the  cytoplasm. 
The  single  cell  thus  becomes  two  cells,  similar  in  all  respects  to  the  parent  cell. 

In  all  higher,  that  is  multicellular  animals,  however,  the  different  functions 
are  distributed  specifically  to  different  cells  and  these  cells  are  specifically 
differentiated  morphologically  for  the  performance  of  these  different  functions. 
There  is,  therefore,  not  the  simple  division  of  a  parent  cell  to  form  two  similar 
daughter  cells,  each  constituting  an  individual,  but  a  differentiation  from  the 
single  original  germ  cell,  the  fertilized  ovum,  of  many  different  kinds  of  cells, 
and  their  specialization  to  form  the  various  tissues  and  organs  which  constitute 
the  adult  body. 

CELL  DIVISION. 

In  the  development  of  the  embryo,  cell  division  of  course  succeeds  fertiliza- 
tion. A  proper  understanding,  however,  of  the  changes  which  take  place  in 
the  ovum  and  in  the  spermatozoon  previous  to  fertilization  requires  the  con- 
sideration of  cell  division  at  this  point. 

Two  types  of  cell  division  are  recognized :  (i)  direct  cell  division  or  amitosis 
and  (2)  indirect  cell  division  or  mitosis. 

(i)  Amitosis  (Fig.  2). — In  this  form  of  cell  division  there  is  no  formation  of 
spin  die  or  of  chromosomes  (see  Mitosis,  p.  4),  the  nucleus  retaining  itsreticular 
structure  during  division.  There  is  first  a  constriction  of  the  nucleus,  followed 
by  complete  division  into  two  daughter  nuclei.  During  the  division  of  the 
nucleus  a  constriction  appears  in  the  cytoplasm.  This  increases  until  the 
cytoplasm  is  divided  into  two  separate  masses  (daughter  cells),  each  containing 


TEXT-BOOK  OF  EMBRYOLOGY. 


a  nucleus.  This  form  of  cell  division,  which  was  considered  by  Remak  and  his 
associates  (1855-1858)  as  the  only  method  by  which  cells  proliferated,  is  now 
known  to  be  of  rare  occurrence.  Flemming  goes  so  far  as  to  state  that  in  the 
higher  animals  amitosis  never  occurs  as  a  normal  physiological  process  in  ac- 
tively dividing  cells,  but  is  rather  to  be  considered  as  a  degeneration  phenomenon 
occurring  in  cells  whose  reproductive  powers  are  on  the  wane.  It  frequently 
results  in  nuclear  division  only,  the  cytoplasm  remaining  undivided,  thus  giving 
rise  to  multinuclear  cells.  It  is  a  common  method  of  cell  division  in  the 
Protozoa. 

(2)  Mitosis. — In  this  form  of  cell  division  the  cell  passes  through  a  series 
of  complicated  changes.      These  changes  occur  as  a  continuous  process,  but 

for  clearness  of  description  it  is  convenient 
to  arbitrarily  subdivide  the  process  into  a 
number  of  phases.  These  are  known  as  the 
prophase,  the  metaphase,  the  anaphase,  and 
the  telophase.  Of  these  the  prophase  in- 
cludes the  changes  preparatory  to  division 
of  the  nucleus;  the  metaphase,  the  actual 
separation  of  the  nuclear  elements;  the 
anaphase,  their  arrangement  to  form  the  two 
daughter  nuclei;  the  telophase,  the  division 
of  the  cytoplasm  to  form  two  daughter  cells 
and  the  reconstruction  of  the  two  daughter 
nuclei. 

PROPHASE  (Fig.  3). — In  actively  divid- 

FIG.  2.— Epithelial  cells  from  ovary  of   ing  cells  the  centrosome,  or,  more  specific- 
cockroach,  showing   nuclei  dividing  ami-      n       ,,  _,   .   , 

toticaiiy.    Wheeler.  ally,  the  centnole,  may  be  double  (Fig.  3, 

A),  having  undergone  division  as  early,  fre- 
quently, as  the  anaphase  of  the  preceding  division  (p.  6).  Each  centnole 
is  surrounded  by  a  clear  area,  the  centrosphere,  from  which  radiate  the 
delicate  astral  rays,  the  whole  being  known  as  the  attraction  sphere  (Fig.  3, 
B,  C,  D).  Connecting  the  two  centrosomes  are  other  delicate  fibrils  forming  a 
structure  known  as  the  central  or  achromatic  spindle  (Fig.  3,  B,  better  developed 
in  C  and  D).  The  two  centrioles  with  their  surrounding  centrospheres,  astral 
rays  and  connecting  spindle,  constitute  the  amphiaster.  If  the  resting  cell 
contains  only  one  centriole,  division  of  the  centnole  with  formation  of  the 
amphiaster  is  usually  the  first  phenomenon  of  mitosis,  the  connecting  central 
spindle  fibers  appearing  as  the  centrioles  move  apart. 

During  or  following  the  formation  of  the.  amphiaster,  important  changes 
occur  in  the  nucleus.  It  increases  somewhat  in  size  and  the  reticulum  charac- 
teristic of  the  resting  nucleus  becomes  converted  into  a  single  long  thread 


THE   CELL  AND   CELL  PROLIFERATION.  5 

(spireme  thread)  arranged  in  a  closed  skein— closed  spireme  (Fig.  3,  B).  This 
soon  becomes  more  loosely  arranged,  the  thread  at  the  same  time  becoming 
shorter  and  thicker  and  frequently  broken,  forming  the  open  spireme.  During 
the  formation  of  the  spireme  Jhe  nucleolus  and  nuclear  membrane  usually 
disappear,  the  nucleoplasm  thus  becoming  continuous  with  the  cytoplasm. 
The  spireme  now  lies  with  the  amphiaster  in  the  general  cell  protoplasm. 
The  morphological  change  from  reticulum  to  spireme  is  apparently  accom- 


FIG.  3. — Diagrams  of  successive  stages  of  mitosis.     Wilson. 

A,  Resting  cell  with  reticular  nucleus  and  true  nucleus;  c,  two  centrioles — the  single  preceding 

one  having  divided  in  anticipation  of  the  division  of  nucleus  and  cell  body. 

B,  Early    prophase.     Chromatin   forming   a    continuous   thread — closed    spireme;  nucleolus    still 

present;  a,  centrioles  surrounded  by  astral  rays  and  connected  by  achromatic  spindle. 

C,  Later  prophase.     Spireme  has   segmented  to  form  chromosomes;   astral  rays  and  achromatic 

spindle  larger  and  more  distinct;  nuclear  membrane  less  distinct. 

D,  End  of  prophase;  ep,  chromosomes  arranged  in  equatorial  plane  of  spindle.    Wl^/ 

panied  by  changes  of  a  chemical  nature,  as  the  spireme  thread  stains  much 
more  intensely  than  do  the  strands  of  the  reticulum. 

The  next  step  is  the  transverse  division  of  the  spireme  thread  into  a  number 
of  segments  (Fig.  3,  C).  These  are  usually  at  first  rod-shaped,  and  are 
known  as  chromosomes.  They  may  remain  rod-shaped  or  the  rods  may 
become  bent  to  form  U's  or  Vs.  Some  chromosomes  are  spheroidal.  The 
most  remarkable  feature  of  the  breaking  up  of  the  spireme  thread  to  form 


6  TEXT-BOOK  OF  EMBRYOLOGY. 

chromosomes  is  that  the  number  of  segments  into  which  the  thread  divides, 
while  differing  for  different  species  of  plants  and  animals,  is  fixed  and  definite 
for  each  particular  species.  For  example,  in  Ascaris  megalocephala — a  very 
convenient  type  for  study  on  account  of  its  simplicity — the  number  of  chro- 
mosomes is  4,  in  the  mouse  20.  In  man  the  number  is  not  known  with  cer- 
tainty, the  most  authoritative  estimate  being  24. 

There  are  thus  at  this  stage  present  in  the  cytoplasm,  two  distinct  though 
closely  related  structures — the  amphiaster  and  the  chromosomes.  These 
together  constitute  the  mitotic  figure.  As  the  chromosomes  form  they  become 
arranged  in  the  equator  of  the  central  spindle,  along  what  is  known  as  the 
equatorial  plane  (Fig.  3,  D).  When,  as  is  frequently  the  case,  the  chromosomes 
are  U-shaped,  the  closed  ends  of  the  loops  lie  toward  the  center,  the  open  ends 
radiating.  Three  sets  of  fibers  can  now  be  distinguished  in  connection  with  the 
centrosomes  (Fig.  3,  C,  D) :  (i)  the  fibers  of  the  central  spindle  connecting 
the  two  centrosomes;  (2)  the  polar  rays  which  radiate  from  the  centriole 
toward  the  periphery  of  the  cell;  (3)  the  mantle  fibers  which  pass  from  the 
centrosomes  to  the  chromosomes. 

The  mitotic  figure  is  at  this  stage  known  as  the  monaster,  and  its  complete 
formation  marks  the  end  of  the  prophase. 

METAPHASE. — The  essential  feature  of  the  metaphase  is  the  longitudinal 
splitting  of  each  chromosome  into  exactly  similar  halves  (Fig.  4,  E),  each  half 
containing  an  equal  amount  of  the  chromatin  of  the  parent  chromosome.  In 
the  case  of  U-  or  V-shaped  chromosomes,  the  splitting  begins  at  the  crown 
and  extends  to  the  open  ends.  The  latter  often  remain  united  for  a  time, 
giving  the  appearance  of  rings  or  loops.  The  significance  of  this  equal  longi- 
tudinal splitting  of  the  chromosomes  is  apparent  when  one  considers  that 
through  this  means  an  exactly  equal  part  of  each  chromosome  and  thus  exactly 
equivalent  parts  of  the  chromatin  of  the  parent  nucleus  are  distributed  to  the 
nucleus  of  each  daughter  cell. 

ANAPHASE. — Actual  division  of  the  chromosomes  having  taken  place,  the 
next  step  is  their  separation  to  form  the  daughter  nuclei.  In  separating,  the 
daughter  chromosomes  pass  along  the  fibers  of  the  central  spindle  (Fig.  4,  F), 
apparently  under  the  guidance  of  the  mantle  fibers,  each  group  toward  its 
respective  centrosome,  around  which  the  chromosomes  finally  become  arranged 
(Fig.  4,  G),  thus  forming  two  daughter  stars.  The  mitotic  figure  is  now 
known  as  the  diaster.  In  actively  dividing  cells  it  is  common  for  the  centriole 
to  undergo  division  at  this  stage,  thus  making  four  centrioles  in  the  cell. 
(Fig.  4,  F,  G.) 

TELOPHASE  (Fig.  4,  H).— This  is  marked  by  division  of  the  cytoplasm, 
usually  in  the  equatorial  plane  of  the  achromatic  spindle,  and  the  reconstruction 
of  the  two  daughter  nuclei.  Each  new  cell  now  contains  a  nucleus,  a  centrosome 


THE   CELL  AND  CELL  PROLIFERATION. 


with  its  aster  (or  two  centrioles  with  asters)  and  one-half  the  achromatic 
spindle.  The  resting  nucleus  is  formed  by  a  reverse  of  the  series  of  changes 
described  as  occurring  in  the  prophase,  the  chromosomes  uniting  end  to  end  to 
form  a  skein  or  spireme,  lateral  buds  appearing  which  anastomose,  thus  giving 
rise  to  the  reticulum  of  the  resting  nucleus.  The  nucleolus  reappears  as 
mysteriously  as  it  disappeared  during  the  prophase  and  the  nuclear  membrane 
is  reformed. 


FIG.  4. — Diagrams  of  successive  stages  of  mitosis.     Wilson. 

E,  Metaphase.     Longitudinal    splitting    of    chromosomes    to    form   daughter  chromosomes,    ep; 

n,  cast-off  nucleolus. 

F,  Anaphase.     Daughter  chromosomes  passing  along  fibers  of  achromatic  spindle  toward  centro- 

somes;   centrioles  again  divided;  if,  interzonal  fibers  of  central  spindle. 

G,  Late  anaphase.     Chromosomes  at  ends  of  spindle;  spindle  fibers  less  distinct;  thickenings  of 

fibers   in    equatorial   plane  indicate  beginning  of  cytoplasmic  plate;  cell  body  beginning  to 
divide;  nucleolus  has  disappeared. 

H,  Telophase.     Cell   body  divided;   chromatic  substance  in  each  daughter  nucleus  as  in  resting 
stage;  nuclear  membrane  and  nucleolus  has  reappeared  in  each  daughter  cell. 

It  is  to  be  noted  that  the  number  of  chromosomes  which  enter  into  the  forma- 
tion of  the  chromatic  reticulum  of  the  resting  nucleus  is  the  same  as  the  number 
of  chromosomes  derived  from  that  nuclear  reticulum  when  the  cell  prepares  for 
mitotic  division.  It  is  thus  probable  that  the  chromosomes  maintain  their  in- 
dividuality even  during  the  resting  stage. 

In  plant  mitosis  the  central  spindle  fibers  show  minute  chromatic  thicken- 


8  TEXT-BOOK  OF  EMBRYOLOGY. 

ings  along  the  plane  of  future  division  of  the  cell,  forming  what  is  known  as  the 
mid-body  or  cell-plate.  This  splits  into  two  layers,  between  which  the  division 
of  the  cell  takes  place.  The  formation  of  a  distinct  cell-plate  in  animal 
mitosis  is  rare.  In  place  of  this  there  is  a  modification  of  the  cytoplasm  along 
the  line  of  future  division,  sometimes  called  the  cytoplasmic  plate. 

As  to  what  may  be  called  the  dynamics  of  mitosis,  there  has  been  much 
controversy,  but  comparatively  little  has  been  definitely  settled. 

It  would  appear  that  in  most  cases  the  centrosome  is  the  active  agent  in 
initiating,  and  possibly  in  further  controlling  the  mitotic  process.  Boveri, 
for  this  reason,  refers  to  the  centrosome  as  the  "dynamic  center"  of  the  cell. 
The  centriole  first  divides  into  two,  around  each  of  which  an  astral  system  of 
fibers  is  formed.  The  origin  of  these  fibers  appears  to  differ  in  different  cells. 
Thus,  in  some  cases — Infusoria,  for  example — the  centrosome  lies  within  the 
nucleus  and  the  entire  mitotic  figure  apparently  develops  from  nuclear  struc- 
tures. In  some  of  the  higher  plants  both  central  spindle  fibers  and  asters 
are  formed  from  the  spongioplasm.  In  still  other  cases — for  example,  the  eggs 
of  Echinoderms — part  of  the  figure  (the  asters)  is  developed  from  the  cytoplasm, 
while  the  fibers  of  the  central  spindle  are  of  nuclear  origin. 

It  must,  however,  be  admitted  that  centrosome  activity  is  not  absolutely 
essential  to  cell  division,  for  there  are  cases  in  which  division  of  the  chromo- 
somes occurs  without  division  of  the  centrosome,  while  in  the  higher  plants 
mitosis  occurs,  although  no  centrosome  can  be  distinguished  at  any  stage  of 
the  process. 

The  behavior  of  the  centrosome  before,  during  and  after  mitosis  varies  in 
different  cells.  In  some  cells  the  centriole  is  apparently  an  integral  part  of 
the  cell,  persisting  throughout  the  resting  stage.  With  it  may  remain  more 
or  less  of  the  aster,  the  whole  constituting  the  already  mentioned  attraction 
sphere.  In  other  cells — for  example,  mature  egg  cells — the  centriole  with 
its  fibrils  apparently  entirely  disappears  during  the  resting  stage. 

In  regard  to  the  origin  of  the  chromatic  portion  of  the  mitotic  figure,  no 
difference  of  opinion  exists,  so  evidently  does  it  arise,  as  already  noted,  from  the 
chromatic  portion  of  the  nuclear  reticulum.  Its  destination  in  the  nuclear 
reticulum  of  the  daughter  cells  is  equally  well  established.  The  details  of  the 
formation  of  the  chromosomes  vary.  Thus  in  some  cases  there  is  no  single 
spireme  thread,  the  spireme  being  segmented  from  its  formation,  each  segment 
of  course  corresponding  with  a  future  chromosome.  In  other  cases  no  spireme 
whatever  is  formed,  the  chromosomes  taking  origin  directly  from  the  nuclear 
reticulum.  In  still  other  cases  the  spireme  while  yet  a  single  thread  splits 
longitudinally  so  that  there  are  two  threads  present,  the  transverse  divisions 
into  chromosomes  taking  place  subsequently. 

As  to  the  time  required  for  the  mitotic  process,  considerable  variation  exists 


THE  CELL  AXD  CELL  PROLIFERATION.  9 

The  process  usually  requires  from  one- half  to  three-quarters  of  an  hour,  but 
may  extend  over  from  two  to  three  hours. 

Mitosis  is  naturally  most  active  wherever  active  growth  of  tissue  is  taking 
place — for  example,  in  embryonic  tissues,  in  granulation  tissue,  in  the  healing 
of  wounds,  in  rapidly  growing  tumors  (usually  an  evidence  of  malignancy). 
The  earlier  generations  of  cells  derived  from  the  fertilized  ovum  are  indifferent 
cells  in  the  sense  that  they  are  capable  of  development  into  any  type  of  tissue 
cells.  As  differentiation  takes  place,  the  cells  assume  more  definite  and  fixed 
types.  With  differentiation,  mitosis  becomes  less  and  less  active  and  cells 
become  incapable  of  producing  cells  of  any  type  other  than  their  own.  Finally, 
the  most  highly  differentiated  (specialized)  cells — for  example,  muscle  cells  and 
nerve  cells — lose  entirely  their  powers  of  reproduction,  and  if  destroyed  are  not 
replaced  by  new  cells  of  the  same  type. 

What  is  known  as  multipolar  or  pluripolar  mitosis  occurs  in  some  of  the 
higher  plants,  less  commonly  in  the  rapidly  growing  connective  tissue  of  healing 
wounds  and  in  cancer  cells.  Such  atypical  mitosis  has  also  been  artificially 
induced  in  rapidly  dividing  cells  by  the  injection  of  chemical  substances  into  the 
tissues.  In  multipolar  mitosis  the  centrosome  divides  into  more  than  two 
daughter  centrosomes  and  not  infrequently  results  in  an  unequal  distribution,  of 
chromatin  to  the  daughter  cells. 


References  for  Further  Study. 

BUCHXER,  P.:  Praktikum  der  Zellenlehre.     Erster  Teil,  Berlin,  1915. 

CONKLIX,  E.  G.:  Karyo kinesis  and  Cytokinesis.  Jour.  Acad.  Nat.  Sci.  of  Philadel- 
phia, Vol.  XII,  1902. 

HEIDEXHAIX,  M.:  Plasma  und  Zelle,  Abteilung  I,  1907,  Abteilung  II,  1911. 

HERTWIG,  O.:  Die  Zelle  und  die  Gewebe.     1908. 

KELLICOTT,  \V.  E.:  General  Embryology,  1913. 

LILLIE,  F.  R.:  A  Contribution  towards  an  Experimental  Analysis  of  the  Karyo  kinetic 
Figure.  Science,  Xew  Series,  Vol.  XXVII,  1908. 

WILSON,  E.  B.:  The  Cell  in  Development  and  Inheritance.     26.  Ed.,  1900. 


CHAPTER  II. 
THE  GERM  CELLS— OVUM  AND  SPERMATOZOON 

It  is  customary,  from  the  biologist's  point  of  view,  to  divide  the  cells  of 
multicellular  animals,  or  metazoa,  into  two  classes:  (i)  the  somatic  cells  and 
(2)  the  germ  cells.  The  somatic  cells  constitute  the  various  tissues  and  organs 
of  the  body  and  take  part  in  the  general  physiological  processes  during  the  life 
of  the  individual  but  perish  without  descendants  when  the  individual  dies. 
The  germ  cells,  on  the  other  hand,  are  confined  to  the  gonads,  or  genital  glands, 
play  no  role  in  the  general  economy  of  the  individual;  but  are  so  specialized 
that  under  proper  conditions  they  give  rise  to  a  new  individual  and  thus  per- 
petuate the  species. 

In  the  entire  vertebrate  series  of  animals,  and  indeed  in  almost  the  whole 
invertebrate  series,  the  development  of  a  new  individual  can  take  place  only 
after  the  union  of  two  germ  cells  produced  by  two  sexually  different  and  mature 
individuals.  These  cells  are  the  egg  (ovum,  ovium)  and  the  sperm  (sperma- 
tozoon, spermium),  the  former  produced  by  the  female,  the  latter  by  the  male. 
They  are  found  in  each  sex  in  special  glands — the  ovum  in  the  ovary  and  the 
spermatozoon  in  the  testis — from  which  they  are  detached  at  definite  times 
during  sexual  maturity.  Prior  to  their  union  to  form  the  starting  point  of  a 
new  individual  they  pass  through  important  preparatory  stages  which  must 
be  considered  along  with  their  general  characteristics. 

THE  OVUM. 

With  the  exception  of  some  neurones,  the  human  ovum  (Fig.  5)  is  the 
largest  cell  in  the  body.  It  is  spherical  in  shape,  measuring  from  0.15  mm.  to 
0.2  mm.  in  diameter,  contains  a  large  spherical  nucleus  and  is  surrounded  by  a 
relatively  thick,  transparent  membrane.  As  seen  in  section  in  the  ovary  it  has 

10 


THE   SEXUAL  ELEMENTS— OVUM  AND   SPERMATOZOON. 


11 


essentially  the  structure  of  a  typical  cell.  Around  the  ovum  and  separated 
from  it  by  a  narrow  cleft — the  perivitelline  space — is  the  zona  pellucida,  a  rather 
thick,  highly  refractive  membrane  which  shows  radial  striations.  These 
striations  are  probably  due  to  the  presence  of  minute  canals  which  penetrate  the 
zona.  It  has  been  suggested  that  these  canals  serve  for  the  passage  of  nutri- 
ment to  the  ovum.  Immediately  outside  of  the  zona  pellucida  the  epithelial 
cells  of  the  Graafian  follicle  are  arranged  radially  in  one  or  two  layers.  These 


Zona 
pellucida 


FIG.  5. — From  a  section  of  the  ovary  of  a  1 2-year  old  girl.  The  primary  oocyte  lies  in  a  large 
mature  Graafian  follicle  and  is  surrounded  by  the  cells  of  the  "germ  hill"  (the  inner  edge  of  which 
is  shown  in  the  upper  left-hand  corner  of  the  figure).  Photograph. 

constitute  the  corona  radiata  (Fig.  5).  Some  investigators  have  described  a 
thin,  delicate  mtelline  membrane  between  the  perivitelline  space  and  the  ovum. 
Others  have  failed  to  observe  this. 

The  egg  protoplasm,  originally  called  the  vitellus,  differs  from  the  pro- 
toplasm of  most  cells  hi  that  it  appears  somewhat  more  opaque  and  coarsely 
granular.  This  appearance  is  due  to  the  fact  that  the  ovum  stores  up  within 
itself  food  stuffs.  These  consist  of  fatty  and  albuminous  substances  which  are 


12 


TEXT-BOOK  OF  EMBRYOLOGY. 


later  utilized  in  the  growth  and  increase  of  the  embryonic  cells.  The  food 
granules— deutoplasm — are  suspended  in  the  cytoplasm.  The  distribution, 
however,  of  these  granules  in  the  human  ovum  is  not  uniform;  a  mass  of  them 
being  found  in  the  center  of  the  cell  surrounding  the  nucleus,  while  an  almost 
clear  zone  of  cytoplasm  forms  the  periphery  of  the  cell. 

The  nucleus  of  the  ovum  occupies  a  position  near  the  center  within  the 
deutoplasm  mass,  though  in  the  ovum  of  a  mature  Graafian  follicle  it  is  almost 
invariably  slightly  eccentric.  It  is  large  proportionately  as  the  ovum  is  large. 
Its  structure  does  not  differ  essentially  from  that  of  any  other  nucleus.  There 
is  a  distinct  nuclear  membrane  enclosing  the  usual  nuclear  structures — the 
nuclear  liquid,  the  network  of  chromatin,  the  achromatic  network  and  a  single 

nudeolus  or  germinal  spot  (p.  2,  Fig.  i).     In 
/-•^  a  fresh  human  ovum  amoeboid  movements 

have  been  observed  in  the  nucleolus.     The 

\ 

•  \      significance  of  the  nucleolus  is  as  little  known 
^jjSiJfc^  5|    as  m  anv  other  cell. 

K  A  centrosome,  though  it  may  be  present, 

has  not  been  observed  in  the  human  ovum. 

A  classification  of  ova  has  been  made 
on  the  basis  of  the  amount  and  distribution 
of  the  yolk;  conditions  which  strongly  affect 
the  subsequent  processes  of  development. 
The  term  meiolecithal  is  used  to  designate 
ova  in  which  the  yolk  granules  are  relatively 
few  (ova  of  Amphioxus,  most  Mammals  in- 
cluding man).  Mesolecithal  ova  are  those 
which  contain  a  moderate  amount  of  yolk 
(Amphibia.)  Ova  which  contain  a  relatively 
large  amount  of  yolk  are  classed  as  foly- 

lecithal  (Reptiles  and  Birds).  In  meiolecithal  eggs  the  yolk  granules  are  as  a 
rule  evenly  distributed  through  the  cytoplasm.  In  mesolecithal  and  polyleci- 
thal  eggs,  on  the  other  hand,  the  yolk  is  unevenly  distributed,  giving  rise  to  a 
condition  known  as  polar  differentiation ;  the  protoplasm  is  in  excess  at  one  pole 
of  the  egg  and  the  deutoplasm  in  excess  at  the  opposite  pole.  Such  ova  are 
spoken  of  as  telolecithal.  The  frog's  egg  is  a  familiar  example  of  this  differ- 
entiation, the  dark  side  of  the  egg  indicating  an  excess  of  cytoplasm.  Inasmuch 
as  deutoplasm  is  generally  heavier  than  cytoplasm,  an  egg  with  polar  differ- 
entiation, if  left  free  to  revolve,  as  in  water,  will  assume  a  definite  position 
with  the  protoplasmic  or  animal  pole  above  and  the  deutoplasmic  or  vegeta- 
tive pole  below.  An  exception  to  this  is  found,  however,  in  the  pelagic  teleost 
eggs,  which  float  with  the  deutoplasmic  pole  upward. 


FIG.  6. — Semidiagrammatic  representa- 
tion of  ovum  of  frog  (Rana  sylvatica). 
The  dark  shading  represents  the  cyto- 
plasmic  pole,  the  light  shading  immedi- 
ately below  represents  the  deutoplasmic 
pole.  The  light  shading  around  the 
ovum  represents  the  gelatinous  sub- 
stance (secondary  egg  membrane). 


THE  SEXUAL  ELEMENTS— OVUM  AND  SPERMATOZOON.  13 

In  the  hen's  egg  the  cytoplasm  and  deutoplasm  are  distinct  and  separate 
with  no  mingling  of  the  two  substances  (Fig.  7).  While  still  in-the  ovary,  the 
egg  consists  of  the  yellow  yolk  in  the  form  of  an  enormously  large  cell  sur- 
rounded by  the  zona  pellucida,  upon  which  lies  a  small  white  spot,  the  so- 
called  germinal  disk.  The  disk  is  3  or  4  mm.  in  diameter  and  consists  of 
finely  granular  protoplasm  with  a  somewhat  flattened  nucleus.  This  disk 


Germinal  disk  (cytoplasm)  White  yolk 


Albumen  ("white"     -^^L  K^T~ Shdl 

Shell  membrane 
(outer  layer) 

Vitelline 

mm  mm*      mmmmm  \     \\ 

Chalaza 

.  -'     " 

White  yolk  ^S^  VB&tMfSj!      \f\    II 


Yellow  yolk  (deutoplasm) 
FIG.  7. — Diagram  of  a  vertical  section  through  an  unfertilized  hen's  egg.     Bonnet. 

alone  gives  rise  to  the  embryo  proper.  All  the  rest  of  the  mass  consisting  of  a 
vast  number  of  spherules  united  by  a  small  amount  of  cement  substance,  is 
simply  nutritive  material  or  deutoplasm  which  is  later  utilized  for  the  nourish- 
ment of  the  embryo.  The  various  structures  surrounding  the  yolk — albumen, 
shell  membrane  and  shell — are  not  strictly  speaking  parts  of  the  ovum,  but  are 
secondary  egg  membranes  secreted  by  different  portions  of  the  oviduct. 

THE  SPERMATOZOON. 

In  marked  contrast  to  the  ovum,  the  spermatozoon  is  one  of  the  smallest  cells 
of  the  body,  being  only  about  fifty  microns  in  length.  The  spermatozoon,  as 
seen  in  the  seminal  fluid,  in  any  of  the  sexual  passages,  or  even  hi  the  lumen  of  a 
seminiferous  tubule,  is  a  true  sexual  element,  since  it  has  passed  through  certain 
processes  which  prepare  it  for  union  with  the  mature  ovum.  (See  Spermatogen- 
esis,  Chap.  III.)  Like  the  ovum  the  spermatozoon  is  an  animal  cell  of  which, 
however,  both  cell  body  and  nucleus  have  undergone  important  modifications. 
The  flagellate  spermatozoon,  of  which  the  human  spermatozoon  is  an  example 
(Fig.  8),  resembles  a  tadpole  in  shape  and  like  the  latter  swims  about  by 
means  of  the  undulatory  movements  of  its  long  slender  flagellum  or  tail.  It 
consists  of  (i)  a  head,  (2)  a  middle-piece  or  body  and  (3)  a  tail. 

i.  THE  HEAD. — This  in  the  human  spermatozoon  is  from  three  to  five 
microns  long  and  about  half  as  broad.  On  side  view  it  appears  oval;  when 


14 


TEXT-BOOK  OF  EMBRYOLOGY. 


Acrosome 


Head 


Body 


End  ring 


Anterior  end  knob 
Posterior  end  knob 

Spiral  fibers 

.Sheath  of 
axial  thread 


seen  on  edge,  it  is  pear-shaped,  the  small  end  being  directed  forward.  It 
consists  mainly  of  nuclear  material  derived  from  the  nucleus  of  the  parent  cell. 
(See  Spermatogenesis.)  A  thin  layer  of  cytoplasm,  the  galea  capitis  or  head- 

cap,  envelops  the  nuclear  material,  while  in 
front  there  is  a  sharp  edge  known  as  the 
apical  body  or  acrosome.  In  contrast  to  the 
nuclear  portion  of  the  head,  which  of  course 
takes  a  basic  stain,  the  acrosome  stains  with 
acid  dyes.  In  some  forms  the  acrosome  is 
much  larger  than  in  man  and  extends 
forward  from  the  head-cap  as  a  long  spear, 
sometimes  barbed — the  perjoratorium.  This 
process  perhaps  assists  the  spermatozoon  in 
clinging  to  or  in  burrowing  its  way  into  the 
ovum.  Many  peculiar  types  of  perfora- 
toria,  for  example,  lance-shaped,  awl- 
shaped,  spoon-shaped,  corkscrew-shaped, 
have  been  described  and  have  given  charac- 
teristic names  to  the  spermatozoa  possessing 
them. 

2.  THE  BODY  in  the  human  sperma- 
tozoon is  cylindrical  and  about  the  same 
length  as  the  head.  It  consists  of  a  deli- 
cately fibrillated  cord,  the  axial  thread,  sur- 
rounded by  a  protoplasmic  capsule.  In 
some  forms  (Mammals)  a  short  clear  por- 
tion, the  neck,  unites  the  head  and  body. 
In  the  neck  there  can  sometimes  be  demon- 
strated an  anterior  end  knob  and  one  or 
more  posterior  end  knobs  to  which  is  attached 
the  axial  -filament.  In  man  and  in  some 
other  forms,  delicate  fibers — spiral  fibers — 
wind  spirally  around  that  portion  of  the 
axial  filament  which  lies  within  the  body. 
At  the  posterior  end  of  the  body,  the  axial 
filament  passes  through  the  end  disk  or  end 
ring. 

3.  THE  TAIL  in  the  human  spermatozoon  is  forty  to  fifty  microns  in  length; 
is  the  direct  continuation  of  the  axial  thread  of  the  body;  and  consists  of  a  main 
segment  thirty-five  to  forty-five  microns  in  length,  and  a  short  terminal 
segment.  As  in  the  body,  the  axial  filament  is  delicately  fibrillated.  Sur- 


Main  segment 
of  tail 


Axial  thread 
Capsule 


Terminal 
filament 


FIG.  8. — Diagram  of  a  human  sperma- 
tozoon.    Meves,  Bonnet. 


THE  SEXUAL  ELEMENTS— OVUM  AND   SPERMATOZOON.  15 

rounding  the  axial  filament  is  a  thin  cytoplasmic  membrane  or  capsule 
continuous  with  that  of  the  body.  In  the  human  spermatozoon  it  is  ap- 
parently structureless;  in  other  forms  it  assumes  curious  shapes  as,  for  example, 
the  so-called  membrana  undulatoria,  or  wavy  membrane  of  Amphibia,  or  the  fine 
membrane  of  some  Insects.^  The  terminal  segment  consists  of  the  axial  fila- 
ment uncovered  by  any  sheath. 

The  significance  of  the  various  parts  of  the  spermatozoon  can  be  best 
understood  by  reference  to  spermatogenesis  (p.  17). 

Comparing  the  spermatozoon  with  a  cell,  the  head  contains  the  nucleus 
while  the  body  contains  the  centrosome.  It  is  these  parts  of  the  spermatozoon 
which  are  essential  to  fertilization.  The  acrosome  and  the  tail  may  therefore 
be  considered  as  accessory  structures  which  serve  to  bring  and  attach  the 
spermatozoon  to  the  ovum. 

Within  the  tubule  of  the  testis  the  spermatozoa  show  no  evidence  of  motile 
power.  In  the  semen,  however,  which  consists  mainly  of  fluid  secretions  of 
the  accessory  sexual  glands,  they  move  about  freely,  as  also  in  the  fluids  of  the 
female  genital  tract.  Their  speed  has  been  estimated  at  from  1.5  to  3.5  mm. 
per  minute  and  enables  them  to  swim  up  through  the  uterus  and  oviduct,  in 
spite  of  the  fact  that  the  action  of  the  cilia  lining  these  tracts  is  against  them. 

The  life  of  the  spermatozoon  within  the  female  genital  tract  is  not  known. 
Moving  spermatozoa  have  been  found  there  seven  to  eight  days  after  coitus. 
In  one  case  reported  of  removal  of  the  tubes,  living  spermatozoa  were  found 
three  and  one-half  weeks  after  coitus. 

References  for  Further  Study. 

COXKLIX,  E.  G.:  Organ -forming  Substances  in  the  Eggs  of  Ascidians.  Biol.  Bull., 
Vol.  VIII,  1905. 

KEIBEL,-F.  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  1910.     Vol.  I,  Chap.  I. 
WALDEYER,  W. :  In  Hertwig's  Handbuch  der  vergleichenden  u.  experimentellen  Entwick- 
elungslehre  der  Wirbeltiere.     Bd.  I,  Teil  I,  1903.     Also  contains  extensive  bibliography. 
WILSON,  E.  B.:  The  Cell  in  Development  and  Inheritance.     2d  Ed.,  1900. 


;  CHAPTER  III. 
MATURATION. 

It  was  stated  in  the  preceding  chapter  that  the  essential  condition  for  the 
production  of  a  new  individual,  in  practically  all  the  animal  kingdom  and  with- 
out exception  among  the  Vertebrates,  was  the  union  of  two  sexually  different 
cells.  Since  the  number  of  chromosomes  is  constant  for  all  the  cells  of  a 
species,  such  a  union  would  cause  a  doubling  of  chromosomes  unless  the  latter 
were  reduced  to  one-half  their  normal  number.  Such  reduction  actually  takes 
place,  and  forms  the  essential  part  of  the  maturation  processes  of  the  germ  cells. 

SPERMATOGENESIS— MATURATION  OF  THE  SPERM. 

The  spermatozoa  arise  from  the  germinal  epithelium  of  the  testis.  In  the 
mammal  (Fig.  9)  this  epithelium  consists  of  two  kinds  of  cells:  (i)  the  support- 
ing cells  (of  Sertoli)  and  (2)  the  spermatogenic  cells  in  various  stages  of  develop- 
ment. Of  the  latter  the  basal  layer  consists  of  small  round  or  oval  cells  which 
are  known  as  spermatogonia.  Internal  to  these  are  the  larger  spermalocytes 
having  large  vesicular  nuclei  with  densely  staining  chromatin.  Between  these 
and  the  lumen  of  the  seminiferous  tubule  are  several  layers  of  small  round  or 
oval  cells,  the  spermatids.  The  spermatids  have  the  reduced  number  of  chromo- 
somes, and  by  direct  transformation  give  rise  to  the  mature  spermatozoa  which 
may  either  lie  free  in  the  lumen  of  the  tubule  or  have  their  heads  embedded  in 
the  supporting  cells  (Fig.  9). 

The  way  in  which  the  maturation  or  reduction  divisions  take  place  in  the 
higher  animals,  such  as  mammals,  has  not  been  definitely  shown  on  account 
of  the  extreme  minuteness  of  the  cells  and  the  difficulty  of  obtaining  suitable 
material.  The  following  account  is  based  on  data  obtained  from  the  study  of 
lower  forms  (amphibia,  fishes,  insects,  Ascaris)  whose  maturation  processes 
have  been  demonstrated  with  great  accuracy.  Ascaris  (Fig.  10)  and  some  of 
the  insects  (Fig.  1 7)  show  the  later  stages  with  remarkable  clearness.  There 
is  no  reason  to  suppose  that  the  maturation  processes  of  the  mammalian  germ 
cells  differ  essentially  from  those  of  lower  forms. 

The  spermatogonia  divide  by  ordinary  mitosis,  each  daughter  cell  receiving 
the  full  or  diploid  number  of  chromosomes.  After  several  generations  some  of 
the  spermatogonia  pass  through  a  period  of  growth  and  are  then  known  as 
primary  spermatocytes.  During  this  period  important  changes  take  place  in 

17 


18 


TEXT-BOOK  OF   EMBRYOLOGY. 


the  nucleus.  The  chromatin  granules  become 
concentrated  into  a  dense  mass  in  which  very 
little  structure  is  made  out  (Fig.  10,  A).  After 
the  period  of  growth  the  nucleus  assumes  again 
the  reticular  appearance.  Then  when  the 
spireme  is  formed  and  segmentation  occurs, 
previous  to  division,  only  the  haploid  or  one- 
half  the  normal  number  of  chromosomes  appears. 
This  seems  to  be  due  to  an  actual  fusion  of 
chromosomes  by  pairs,  such  fusion  occurring 
during  the  period  of  growth  and  being  known 
as  synapsis  of  chromosomes.  In  some  cases 
the  double  nature  of  the  chromosomes  is  still 
visible  while  in  other  cases  the  fusion  is  com- 
plete. 

The  fused  chromosomes  now  prepare  for 
division.  However,  instead  of  dividing  longi- 
tudinally into  two  parts,  a  double  splitting 
occurs  and  each  chromosome  is  divided  into 
four  elements.  Such  a  quadruple  chromosome 
is  termed  a  tetrad  (Fig.  10,  E,  F,  G).  Since 
each  tetrad  represents  a  double  chromosome, 
the  number  of  tetrads  in  any  species  will  be 
equal  to  one-half  its  normal  number  of  chro- 
mosomes. The  tetrads  arrange  themselves  in 
the  equatorial  plane  of  the  spindle  and  cell 
division  begins  (Fig.  10,  G).  Each  tetrad  is 
separated  into  two  dyads,  and  then  one  dyad 
from  each  tetrad  goes  to  each  of  the  two  re- 
sulting daughter  cells  or  secondary  spermato- 
cytes (Fig.  10,  H).  A  new  spindle  is  formed 
in  each  of  the  secondary  spermatocytes  and 
the  cells  divide  again,  without  the  return  of 
the  nucleus  to  the  resting  stage.  The  dyads 
go  to  the  equatorial  plane.  Each  dyad  is 
separated  into  two  monads,  each  daughter 
cell  or  spermatid  receiving  one  monad  from 

1-8,  Spermatogonia  lying  close  to  the 

basement  membrane  and  multiplying 

by  ordinary  mitosis.  9-16,  Spermatogonia  during  period  of  growth,  resulting  in  primary  spermato- 
cytes. 17,  18,  19,  Primary  spermatoscyte  dividing.  20,  Secondary  spermatocytes.  21,  Second- 
ary spermatocytes  dividing,  resulting  in  spermatids  (22-25).  26-31,  Transformation  of  spermatids 
into  spermatozoa,  a  few  of  which  are  seen  fully  formed  (32). 


MATURATION. 


19 


each  dyad  (Fig.  10,  7,  K,  L).  A  primary  spermatocyte  gives  rise  therefore  to 
four  spermatids  in  which  the  number  of  chromosomes  is  reduced  to  one-half 
the  normal  (Fig.  io,Z). 

After  the  last  spermatocyte  division  and  the  resulting  formation  of  the 
spermatid,  the  nucleus  of  the  latter  acquires  a  membrane  and  intranuclear  net- 


FIG.  10. — Reduction  of  chromosomes  in  spermatogenesis  in  Ascaris  megalocephala  (bivalens). 
Brauer,  Wilson.  A — G,  Successive  stages  in  the  division  of  the  primary  spermatocyte.  The  original 
reticulum  undergoes  a  very  early  division  of  the  chromatin  granules  which  then  form  a  doubly  split 
spireme  (5).  This  becomes  shorter  (C),  and  then  breaks  in  two  to  form  the  2  tetrads  (D,  in  p'rofile, 
E,  on  end).  F,  G,  H,  First  division  to  form  2  secondary  spermatocytes,  each  receiving. 2  dyads.  /, 
Secondary  spermatocyte.  /,  Kt  The  same  dividing.  Z,,  Two  resulting  spermatids,  each  containing 
2  single  chromosomes. 

work,  thus  passing  into  the  resting  condition.  Without  further  division  the 
spermatid  now  becomes  transformed  into  a  spermatozoon.  This  is  accomplished 
by  rearrangement  and  modification  of  its  component  structures  (Fig.  1 1).  The 
ccntrosome  either  divides  completely,  forming  two  centrosomes,  or  partially, 
forming  a  dumb-bell-shaped  body  between  the  nucleus  and  the  surface  of  the 


20  TEXT-BOOK   OF  EMBRYOLOGY. 

cell.  The  nucleus  passes  to  one  end  of  the  cell  and  becomes  oval  in  shape. 
Its  chromatin  becomes  very  compact  and  is  finally  lost  in  the  homogeneous 
chromatin  mass  which  forms  the  greater  part  of  the  head  of  the  spermatozoon. 
Both  centrosomes  apparently  take  part  in  the  formation  of  the  middle  piece. 
The  one  lying  nearer  the  center  becomes  disk-shaped  and  attaches  itself  to  the 
posterior  surface  of  the  head.  The  more  peripheral  centrosome  also  becomes 
disk-shaped  and  from  the  side  directed  away  from  the  head  a  long  delicate 


Head 

Anterior  end  knob 
Posterior  end  knob 


Head 

,  Anterior  end  knob 
Posterior  end  knob 
-  End  ring 


Nucleus 

Cytoplasm 
Proximal  centrosome 


Distal  centrosome 


Tail 


FIG.    ii. — Transformation  of    a   spermatid   into  a   spermatozoon    (human).     Schematic. 

Meves,  Bonnet. 

thread  grows  out — the  axial  filament.  The  central  portion  of  the  outer  cen- 
trosome next  becomes  detached  and  in  Mammals  forms  a  knob-like  thickening 
— end  knob — at  the  central  end  of  the  axial  filament.  In  Amphibians  this  part 
of  the  outer  centrosome  appears  to  pass  forward  and  to  attach  itself  to  the  inner 
centrosome.  In  both  cases  the  rest  of  the  outer  centrosome  in  the  shape  of  a 
ring  passes  to  the  posterior  limit  of  the  cytoplasm.  As  the  two  parts  of  the 
posterior  centrosome  separate,  the  cytoplasm  between  them  becomes  reduced 
in  amount,  at  the  same  time  giving  rise  to  a  delicate  spiral  thread — the  spiral 


MATURATION. 


21 


filament — which  winds  around  the  axial  filament  of  the  middle  piece.  Mean- 
while the  axial  filament  has  been  growing  in  length  and  part  of  it  projects  be- 
yond the  limits  of  the  cell.  The  cytoplasm  remaining  attached  to  the  anterior 
part  of  the  filament  surrounds  it  as  the  sheath  of  the  middle  piece.  In  Mam- 
mals there  appears  to  be  more  cytoplasm  than  is  needed  for  the  formation  of 
the  sheath  of  the  middle  piece,  and  a  large  part  of  it  degenerates  and  is  cast 
aside.  The  sheath  which  surrounds  the  main  part  of  the  axial  filament  appears 
in  some  cases  at  any  rate  to  develop  from  the  filament  itself.  The  galea  capitis 
or  delicate  film  of  cytoplasm  which  covers  the  head  is  undoubtedly  a  remnant 
of  the  cytoplasm  of  the  spermatid. 

The  developing  spermatozoa  lie  with  their  heads  directed  toward  the  base- 
ment membrane,  and  attached,  probably  for  purposes  of  nutrition,  to  the  free 
ends  of  the  Sertoli  cells  (Fig.  9).  Their  tails  often  extend  out  into  the  lumen 
of  the  tubule.  When  fully  developed  they  become  detached  from  the  Sertoli 
cells  and  lie  free  in  the  lumen  of  the  tubule. 


MATURATION  OF  THE  OVUM. 


The  female  germ  cell,  before  it  is  fertilized,  goes  through  a  process  of  matu- 
ration similar  to  that  of  the  male  germ  cell.     The  result  is  essentially  the  same 


m.pn. 


FIG.  12. — From  sections  of  ova  of  the  mouse,  showing  three  stages  in  the  maturation  process. 

A,  Ovum  showing  prophase  of  maturation  division.    /,  fat;  z.p.,  zona  pellucida. 

B,  Ovum  showing  maturation  spindle  with  chromatin  segments  undivided. 

C,  Ovum  showing  diaster  stage  of  maturation  division,  formation  of  ist  polar  body  (p.b.),  and  sperm 

nucleus  (male  pronucleus,  m.pn.)  just  after  its  entrance.    Sobotta. 

the  mature  ovum  contains  a  reduced  number  of  chromosomes.  There  is  this 
difference,  however,  that  while  the  chromatin  elements  are  distributed  equally 
during  the  reduction  divisions,  one  cell  only  retains  practically  all  the  cytoplasm 
and  deutoplasm  present  in  the  primary  oocyte.  This  cell  becomes  the  func- 
tional ovum  while  the  other  cells  are  pinched  off  as  minute  bodies,  containing 
but  little  of  the  cytoplasm,  which  are  known  as  polar  bodies  and  eventually 
degenerate  and  die  (Figs.  12  and  13). 

The  early  maturation  stages  of  the  female  sex  cell  are  very  similar  to  those 


22  TEXT-BOOK  OF  EMBRYOLOGY. 

of  the  male.  The  oogonia  contain  the  diploid  number  of  chromosomes  and 
divide  by  ordinary  mitosis.  After  several  generations  they  pass  through  a 
period  of  growth  and  are  then  known  as  primary  oocytes.  During  the  growth 
period  there  occurs  a  condensation  of  the  chromatin,  and  synapsis  of  the  chro- 
mosomes probably  takes  place  at  this  time.  The  nucleus  then  resumes  its 
reticular  structure.  Following  this  the  spireme  is  formed,  preparatory  to  divi- 
sion, and  segments  into  the  haploid  number  of  chromosomes.  From  this  stage  the 
process  varies  somewhat  in  different  animals.  In  Ascaris,  whose  diploid  num- 
ber of  chromosomes  is  four,  both  maturation  divisions  occur  after  the  sperm 
has  entered  the  egg  and  lies  embedded  there  as  the  male  pronucleus  (Fig.  14). 
An  achromatic  spindle  forms  near  the  surface  of  the  ovum  and  the  two  tetrads 
go  to  the  equatorial  plane  (Fig.  14,  E).  Each  tetrad  separates  into  two  dyads, 
and  one  dyad  from  each  tetrad  passes  into  a  small  mass  of  cytoplasm  which 
becomes  detached  from  the  egg  cell  as  the  first  polar  body  (Fig.  14,  F,  G,  H). 


FIG.  13. — From  sections  of  ova  of  the  mouse,  showing  the  polar  bodies  (p.b.)  and  three  stages  of  the 
male  (m.pn.)  and  female  (J.pn.)  pronuclei.    Sobotta. 

A  new  spindle  forms  without  the  return  of  the  nucleus  to  the  resting  stage,  and 
each  dyad  divides  into  two  monads.  The  second  polar  body  is  now  given  off  in 
the  same  manner  as  the  first.  One  monad  from  each  dyad  passes  into  a  small 
mass  of  cytoplasm  and  is  separated  from  the  egg  cell  (Fig.  14,  H,  I,'J,  K). 
The  maturation  process  is  now  complete.  The  nucleus  of  the  mature  ovum 
contains  the  haploid  number  of  chromosomes  and  is  ready  for  union  with  the 
male  pronucleus. 

The  maturation  of  the  mouse  ovum,  recently  described  by  Mark  and  Long, 
may  be  taken  as  an  example  of  mammalian  maturation.  The  diploid  number 
of  chromosomes  is  twenty,  but  when  the  growth  of  the  primary  oocyte  is  com- 
pleted and  the  cell  prepares  for  division  only  ten  chromosomes  are  present. 
Each  chromosome  is  V-shaped  and  shows  the  structure  of  a  tetrad.  While 
still  in  the  Graafian  follicle  the  first  polar  body  is  given  off  and  lies  as  a  small 
globule  beneath  the  zona  pellucida  (Fig.  13,  A).  The  egg  cell  and  the  first 
polar  body  constitute  secondary  oocytes,  comparable  with  the  secondary  sper- 


MATURATION. 


23 


matocytes  of  the  male.     The  egg  now  leaves  the  ovary  and  reaches  the  oviduct. 
Jf  the  ovum  is  fertilized,  another  spindle  forms  and  a  second  polar  body  is 


FiG.i4. — Maturation  of  the  ovum  of  Ascaris  megalocephala  (bivalens).  Boveri,  Wilson.  A, 
The  ovum  with  the  spermatozoon  just  entering  at  x*  ;  the  egg  nucleus  contains  2  tetrads  (one  not 
clearly  shown),  the  somatic  number  of  chromosomes  being  4.  B,  Tetrads  in  profile.  C,  Tetrads 
on  end.  D,  E,  First  spindle  forming.  F,  Tetrads  dividing.  G,  First  polar  body  formed,  containing 
2  dyads;  2  dyads  left  in  the  ovum.  H,  7,  Dyads  rotating  in  preparation  for  next  division.  /, 
Dyads  dividing.  K,  Each  dyad  divided  into  2  single  chromosomes,  thus  completing  the  reduction, 

given  off.  The  nucleus  of  the  mature  ovum  or  female  pronucleus,  with  the 
haploid  number  of  chromosomes,  is  now  ready  for  union  with  the  male 
pronucleus. 


24 


TEXT-BOOK  OF  EMBRYOLOGY. 


Comparing  maturation  in  the  male  and  female  sex  cells  (Fig.  16),  it  is  to  be 
noted  that  the  spermatogonia  and  oogonia  proliferate  by  ordinary  mitosis, 
maintaining  the  somatic  or  diploid  number  of  chromosomes  up  to  a  certain 
period  in  their  life  history.  They  then  enter  upon  a  period  of  growth  in  size, 
resulting  in  primary  spermatocytes  and  primary  oocytes  (Fig.  16).  When 
these  prepare  for  division  the  nuclear  reticulum  in  each  case  resolves  itself  into 
the  haploid  number  of  chromosomes.  During  division  this  reduced  number  is 
given  to  each  resulting  secondary  spermatocyte  or  oocyte. 

There  is,  however,  this  marked  peculiarity  about  the  division  of  the  primary 
oocyte,  that  while  the  division  of  the  nuclear  material  is  equal  the  division  of  the 
cytoplasm  is  very  unequal,  most  of  the  latter  remaining  in  one  cell,  the  secondary 


FiG.  15. — From  section  of  ovum  (primary  oocyte)  of  the  mouse,  showing  first  maturation 
spindle.  Note  the  12  chromatin  segments,  the  somatic  number  of  chromosomes  being  24.  The 
ovum  is  surrounded  by  the  zona  pellucida  (z.p.)  and  the  corona  radiata.  Sobotta. 

oocyte  proper.  The  other  cell,  very  small  owing  to  its  lack  of  cytoplasm,  is 
extruded  from  the  oocyte  proper  as  the  first  polar  body  (Fig.  16).  The  same 
condition  obtains  in  the  next  division.  One  cell,  the  mature  ovum,  retains 
most  of  the  cytoplasm,  the  other  being  detached  as  the  second  polar  body  (Fig. 
16).  In  some  cases  the  first  polar  body  also  divides.  Thus  the  primary  oocyte 
gives  rise  to  three  or  four  cells,  each  of  which  has  the  reduced  number  of  chromo- 
somes. One  of  them  becomes  the  mature  ovum,  the  others  are  cast  off  as 
apparently  useless  and  eventually  die.  The  primary  spermatocyte,  on  the  other 
hand,  gives  rise  to  four  functioning  cells  which  are  equal  in  cytoplasmic  as  well 
as  in  chromatin  content  (Fig.  16). 

The  apparent  difference  between  maturation  of  the  male  and  female  sex 


MATURATION. 


25 


cells — the  single  functional  cell  in  the  female  as  contrasted  with  four  in  the  male 
— loses  some  of  its  character  when  one  notes  that  in  some  forms  the  polar  bodies 
are  not  so  rudimentary  as  is  generally  the  case.  Thus  in  certain  forms  one  or 
more  of  the  polar  bodies  may  develop  into  cells  very  similar  to  the  mature  egg- 
cell,  may  be  penetrated  by  spermatozoa,  and  may  even  be  fertilized  and  proceed 
a  short  distance  in  segmentation.  There  is  perhaps  warrant  for  considering 
the  polar  bodies  ar  rudimentary  or  abortive  ova. 

The  time  of  formation  of  the  polar  bodies  varies  in  different  animals*     In 
a  few  (Echinoderms)  they  are  formed  before  the  sperm  enters  the  egg.     In 


Oogonia 


Primary 
oocyte 


Secondary 
oocyte 

Mature 
ovum 


A 

Spermatogonia 

.  / 

\ 

A  /\ 

Proliferation 

A  A 

t\  l\ 

/'  A  A  \ 

Primary 
spermatocyte 

A 

Growth 
Secondary 
spermatocyte 

/ 

(X 

....  A 

Spermatid 

/ 

\  l\ 

w  <\ 

1 

Prolifera- 
tion 


Growth 


Maturation 


Trans- 
formation 


FIG.  16. — Diagrams  representing  the  histogenesis  of  (a)  the  female  sex  cells  and  (6)  the  male  sex 

cells.     Modified  from  Boveri. 

Ascaris  they  are  both  formed  after  the  entrance  of  the  sperm.  In  other  forms, 
like  the  mouse,  the  first  polar  body  is  formed  while  the  egg  is  still  in  the  Graafian 
follicle,  the  second  one  after  the  entrance  of  the  sperm. 

From  the  data  in  the  above  description  it  is  evident  that  the  phenomena  of 
maturation  are  essentially  similar  in  the  male  and  female  sex  cells.  In  the 
female  two  or  three  of  the  cells  are  indeed  abortive,  probably  in  order  to  insure 
a  large  amount  of  food  material  to  the  functioning  ovum;  but  the  result,  the 
reduction  of  the  number  of  chromosomes  in  the  mature  sex  cell  to  one-half  the 
number  characteristic  of  other  cells  of  the  species,  is  always  the  same. 


Significance  of  Mitosis  and  Maturation. 

The  earlier  investigators  regarded  maturation  merely  as  a  means  of  reducing 
the  number  of  chromosomes  in  the  mature  germ  cells,  so  as  to  prevent  a  dou- 


26  TEXT-BOOK   OF  EMBRYOLOGY. 

bling  of  chromatin  material  at  the  subsequent  fertilization.  This,  however, 
seems  to  be  but  a  minor  object  of  maturation.  As  a  matter  of  fact,  the  reduc- 
tion of  the  chromatin  mass  is  not  one-half  but  three-quarters  and  even  more.  It 
is  also  well  known  that  the  chromatin  mass  increases  or  diminishes  under  cer- 
tain conditions  during  the  life  history  of  a  cell. 

The  chief  significance  of  maturation  is  to  be  considered  rather  from  the 
standpoint  of  heredity.  Modern  biologists  believe  that  the  chromatin  particles 
are  the  bearers  of  the  hereditary  qualities  of  the  cell.  During  mitosis  the  chro- 
matin granules  arrange  themselves  in  a  continuous  thread,  the  spireme,  which 
differs  qualitatively  in  different  regions.  The  chromosomes,  which  are  only 
segments  of  the  spireme,  likewise  differ  from  end  to  end.  In  ordinary  mitosis 
these  chromosomes  split  longitudinally,  half  of  each  chromosome  going  to  each 
of  the  resulting  daughter  cells.  This  is  an  equational  division  in  which  the 
chromatin  material  is  exactly  halved. 

In  maturation,  however,  a  synapsis  of  the  chromosomes  takes  place,  the 
latter  fusing  in  pairs.  The  chromosomes  of  each  pair  are  probably  separated 
again  in  one  of  the  subsequent  maturation  divisions,  the  reduction  division. 
If  the  chromosomes  are  qualitatively  different,  then  the  mature  germ  cells  re- 
sulting from  this  division  will  be  of  two  different  kinds,  varying  more  or  less 
in  their  content  of  hereditary  factors.  Experimental  evidence  confirms  this 
interpretation  of  maturation. 

There  is  another  interesting  point  to  be  considered.  The  recent  work  of 
cytologists  leads  to  the  assumption  that  the  fusion  of  chromosomes  during  syn- 
apsis is  not  a  matter  of  chance,  but  takes  place  in  a  very  definite  manner.  The 
chromosomes  in  the  primordial  germ  cells  seem  to  form  a  series  of  homologous 
pairs  the  members  of  which  fuse  during  synapsis.  The  individual  pairs  can 
often  be  distinguished  from  other  pairs  by  differences  in  shape  or  size.  There 
is  much  evidence  to  support  the  belief  that  each  pair  consists  of  one  paternal 
and  one  maternal  chromosome,  which  had  been  brought  together  at  the  ante- 
cedent fertilization.  This  seems  to  indicate  also,  as  mentioned  on  page  7, 
that  the  chromosomes  retain  their  identity  even  when  resolved  into  the  chro- 
matic reticulum  of  the  resting  nucleus.  The  reduction  division  will  separate  the 
fused  chromosomes,  and  the  resulting  mature  germ  cells  will  be  either  paternal 
or  maternal  in  their  chromatic  constitution.  The  maturation  processes  there- 
fore produce  a  segregation  of  the  paternal  and  maternal  chromosomes. 

The  cytological  data  described  above,  which  support  and  in  turn  are  sup- 
ported by  a  great  mass  of  experimental  evidence,  illustrate  Mendel's  "law  of 
segregation."  This  law  is  that  "the  units  contributed  by  the  two  parents 
separate  in  the  germ  cells  without  having  had  any  influence  upon  each  other." 
For  instance,  when  a  mouse  with  gray  coat  color  is  mated  with  a  mouse  with 
black  coat  color,  one  parent  contributes  a  unit  for  gray  and  the  other  a  unit 


MATURATION. 


27 


for  black.  These  units  will  separate  during  the  maturation  of  the  germ  cells, 
and  the  resulting  spermatozoa  and  ova  will  again  recover  the  pure  paternal  or 
maternal  units. 

Sex  Determination. 

In  the  great  bulk  of  cytological  and  experimental  studies  of  recent  years 
there  is  abundant  evidence  for  the  belief  that  certain  chromosomes  play  an 


FIG.  17. — Stages  in  the  spermatogenesis  of  a  grasshopper  (Stenobothrus  viridulus).  Meek,  i, 
Spermatogonium  in  process  of  division,  having  17  chromosomes  (8  pairs  and  one  odd).  2,  Repre- 
senting growth  period  of  spermatogonium.  3-6,  Division  of  the  primary  spermatocytes — sixteen  of 
the  chromosomes  are  paired  while  the  "accessory"  has  no  mate  and  passes  as  a  whole  to  one  of  the 
two  secondary  spermatocytes.  7-8,  Division  of  the  secondary  spermatocyte  with  the  odd  chromo- 
some, the  latter  splitting  and  giving  one-half  to  each  resulting  spennatid.  x,  "Accessory"  chromo- 


some. 


important  part  in  the  determination  of  sex.  In  the  grasshopper  (Stenobothrus 
viridulus)  the  somatic  number  of  chromosomes  in  the  male  is  seventeen  and  in 
the  female  eighteen.  Owing  to  the  odd  number  there  is  an  unusual  complica- 
tion in  the  maturation  of  the  male  germ  cell.  When  synapsis  occurs  eight  pairs 


28 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  chromosomes  are  formed  but  the  odd  chromosome,  which  can  usually  be 
distinguished  by  its  appearance,  is  left  without  a  mate.  At  the  first  maturation 
division  this  univalent  chromosome  does  not  divide  but  passes  as  a  whole  to  one 
of  the  two  resulting  cells,  thus  giving  two  kinds  of  secondary  spermatocytes 
(Fig.  17,  4  and  5,  x).  When  the  secondary  spermatocytes  divide,  however,  the 
odd  chromosome  in  one  of  them  also  divides  like  the  other  chromosomes,  each 
of  the  resulting  spermatids  receiving  one-half  (Fig.  17,  7  and  8,  x).  Thus  two 
kinds  of  sperms  are  formed  in  equal  numbers,  containing  respectively  eight  and 
nine  chromosomes.  The  odd  chromosome  is  also  known  as  the  accessory  or 
X-chromosome. 


Germinal 

epithelium 


—      kPll&LUm                                         MV-V-  ."*afi 

granulosum                       ^s&ss.^ 

^*»3* 

^^P 

^^cx 

-*^Po\ 

-  ~'  ~~~.  .'-  ^ 

Tunica  albuginea 

x;->%" 

V^^i-z'''. 
s,   JPp^ 

Germ  hill             Theca  folKcuii 
with  ovum        (vascular  layer)  

^3 

iw^ 

EKIK  I 

WM  *; 

1 
1 

VHvfT   >  i 

ml 

Theca  folliculi  (fibrous  layer)  - 

&  -••"• 

at    ••; 

Kf.  ••i'J'i 

Stratum  granulosum 

/.^'•//'^ 

1 

../^>-  "  '. 

s. 

i^^               ^s%£. 

tjS&ii 

, 

FIG.  1 8. — From    section   of   human   ovary,  showing   mature    Graafian  follicle    ready  to  rupture. 

Kollmann's  Atlas. 

In  the  ovum  no  such  complication  arises,  there  being  two  "accessory" 
chromosomes  which  unite  in  synapsis.  All  the  mature  ova  will  therefore  con- 
tain nine  chromosomes.  As  a  result,  there  are  two  combinations  possible  when 
the  male  and  female  sex  cells  unite :  an  ovum  may  be  fertilized  by  a  sperm  con- 
taining either  eight  or  nine  chromosomes.  In  the  first  case  the  somatic  number 
in  the  fertilized  egg  will  be  seventeen  and  the  egg  will  develop  into  a  male.  In 
the  second  case  the  somatic  number  will  be  eighteen  and  the  resulting  individual 
will  be  a  female.  In  the  example  given,  therefore,  the  presence  or  absence 
of  the  "accessory"  or  odd  chromosome  will  determine  the  nature  of  the  sex 
produced. 

The  presence  of  "accessory"  chromosomes  has  been  demonstrated  in  many 
Invertebrates,  especially  Insects.  Recently  they  have  also  been  described  in 


MATURATION. 


29 


several  vertebrates  such  as  the  rat,  fowl,  guinea-pig,  and  even  man.  In  many 
cases  the  "accessory"  chromosome  of  the  male  germ  cell  has  a  mate  which 
differs,  however,  in  some  way  (size,  appearance,  etc.)  and  is  designated  the  Y- 
chromosome.  An  ovum  fertilized  by  a  spermatozoon  containing  the  Y-chro- 
mosome  will  give  rise  to  a  male ;  if  fertilized  by  one  containing  the  X-chromosome 
the  egg  will  develop  into  a  female. 

There  are  many  cases,  particularly  among  parthenogenetic  forms,  where 
sex  cycles  arise,  which  cannot  be  explained  by  chromosomal  behavior.  In 
these  cases  nutrition  seems  to  play  an  important  part  in  determining  the  sex  of 
the  individual.  But  as  to  the  great  majority  of  forms  investigated,  the  weight 
of  evidence  supports  the  view  that  the  chromosomes  are  the  chief  agents  in  sex 
determination. 

OVULATION  AND  MENSTRUATION. 

By  ovulation  is  meant  the  periodic  discharge  of  the  ovum  from  the  Graafian 
follicle  and  ovary.  By  menstruation  is  meant  the  periodic  discharge  of  blood 


FIG.  19. — Showing  ovary  opened  by  longitudinal  incision.  The  ovum  has  escaped  through  the 
tear  in  the  surface  of  the  ovary.  The  cavity  of  the  follicle  is  filled  with  a  clot  of  blood  (corpus  hacmor- 
rhagicum)  and  irregular  projections  composed  of  lutein  cells.  Kollmann's  Atlas. 

from  the  uterus  associated  with  structural  changes  in  the  uterine  mucosa.  The 
two  phenomena  are  usually  associated  although  either  may  occur  independently 
of  the  other.  They  normally  occur  every  twenty-eight  days.  That  ovulation 
and  menstruation  are  not  necessarily  dependent  upon  each  other  and  that  either 
may  occur  without  the  other  has  been  proved  by  a  number  of  observations; 
thus  the  occurrence  of  fertilization  during  lactation  when  the  menstrual  func- 
tion is  in  abeyance;  the  occurrence  of  impregnation  in  young  girls  before  the 


30 


TEXT-BOOK  OF   EMBRYOLOGY. 


onset  of  the  menstrual  periods  and  in  women  a  number  of  years  after  the  meno- 
pause. Leopold  reports  the  examination  of  twenty-nine  pairs  of  ovaries  on 
successive  days  after  menstruation  and  the  finding  of  Graafian  follicles  just 
ruptured  or  just  ready  to  rupture  on  the  eighth,  twelfth,  fifteenth,  eighteenth, 
twentieth  and  thirty-fifth  days.  He  reports  also  five  cases  in  which  there  were 
no  evidences  of  ovulation  during  menstruation. 

At  the  time  of  ovulation  the  mature  follicle,  which  has  a  diameter  of  8  to  12 
mm.,  occupies  the  entire  thickness  of  the  ovarian  cortex,  its  theca  being  in  con- 
tact with  the  tunica  albuginea  (Fig.  18).  Thinning  of  the  follicular  wall  nearest 
the  surface  of  the  ovary,  and  increase  in  the  amount  of  the  liquor  folliculi,  thus 


Point  of  rupture 


Lutein  cells 


Corpus  haemorrhagicum 


Blood  vessel  of  theca 


Cavity  of  follicle 


Theca  folliculi 


Ovarian  stroma 


Stratum  granulosum 


FIG.  20. — From  section  of  human  ovary,   showing  early  stage  in  formation  of  corpus  luteum. 

Kollmann's  Alias. 

causing  increased  intrafollicular  pressure,  are  followed  by  the  rupture  of  the 
follicle  through  the  surface  of  the  ovary  and  the  escape  of  the  ovum  together 
with  the  liquor  folliculi  and  some  of  the  follicular  cells. 

The  escaped  ovum  normally  passes  into  the  fimbriated  end  of  the  Fallopian 
tube  and  so  to  the  uterus.  In  exceptional  cases  it  may  remain  in  the  tube  after 
fertilization  and  so  give  rise  to  a  tubal  pregnancy,  or,  falling  into  the  abdominal 
cavity  and  becoming  there  fertilized,  to  an  abdominal  pregnancy.  Both  are 
known  as  ectopic  gestations. 

As  the  ovum  escapes  from  the  follicle  there  is  more  or  less  bleeding  into  the 
follicle  from  the  torn  vessels  of  the  theca.  Closure  of  the  opening  in  the  follicle 
results  in  a  closed  cavity  containing  a  blood  clot,  the  corpus  hamorrhagicum, 


MATURATION. 


31 


(Fig.  19)  which  then  becomes  gradually  transformed  into  the  corpus  luteum. 
Large  cells  containing  fat  droplets  and  yellow  pigment  (lutein  granules)  appear 
around  the  blood  clot  and  then  increase  in  number  until  they  replace  the  clot 
(Figs.  20  and  21).  These  cells,  which  are  called  lutein  cells,  are  considered  by 
some  as  derivatives  of  the  connective-tissue  cells  of  the  theca  folliculi  and  by 
others  as  derivatives  of  the  stratum  granulosum  of  the  follicle.  The  latter 
view  seems  the  more  probable.  Ingrowth  of  strands  of  connective  tissue  fol- 

Point  of  rupture 


Connective  tissue 


Connective  tissue 
from  theca 


Theca  folliculi 


Remnant  of  corpus 
hsemorrhagicum 


Blood  vessels 
of  theca 


FIG.  21. — From   section  of  human  ovary,  showing   later  stage  of  corpus  luteum  than  Fig.  20. 

Kollmann's  Atlas. 

lows  the  development  of  the  lutein  cells  and  gradually  this  connective  tissue 
replaces  the  mass  of  lutein  cells  which  undergo  degeneration  and  absorption. 
The  corpus  luteum  thus  gives  way  to  dense  connective  tissue,  the  corpus  albicans. 
This  body  persists  for  a  long  period,  gradually  retracting  to  an  almost  micro- 
scopic scar. 

The  rapidity  with  which  the  changes,  both  constructive  and  destructive, 
take  place  in  the  corpus  luteum,  appears  to  be  largely  dependent  upon  whether 
the  egg  which  escaped  from  the  follicle  is  or  is  not  fertilized.  If  ovulation  is 


32  TEXT-BOOK   OF  EMBRYOLOGY. 

not  followed  by  fertilization  the  corpus  luteum  reaches  the  height  of  its  develop- 
ment in  about  twelve  days,  and  within  a  few  weeks  has  almost  wholly  disap- 
peared. If,  on  the  other  hand,  pregnancy  supervenes,  the  corpus  luteum  be- 
comes much  larger,  does  not  reach  its  maximum  development  until  the  fifth  or 
sixth  month  and  is  still  present  at  the  end  of  pregnancy.  The  above  differences 
have  led  to  the  distinction  of  the  corpus  luteum  of  pregnancy  or  the  true  corpus 
luteum,  and  the  corpus  luteum  of  menstruation,  or  the  false  corpus  luteum,  al- 
though there  are  no  actual  microscopic  differences  between  the  two. 

References  for  Further  Study. 

BOVERI,  T.:  Zellstudien.     Jena,  1887-1901. 

BUCHNER,  P.:  Praktikum  der  Zellenlehre,  Erster  Teil,  Berlin,  1915. 

CHILD,  C.  M.:  Studies  on  the  Relation  between  Amitosis  and  Mitosis.  Biolog.  Bull., 
Vol.  XII,  Nos.  2,  3,  4;  Vol.  XIII,  No.  3,  1907. 

CONKLIN,  E.  G.:  The  Embryology  of  Crepidula.     Jour,  of  Morphol.,  Vol.  XIII,  1897. 

CRAGIN,  E.  B.:  Text-book  of  Obstetrics,  1915. 

HERTWIG,  R.:  Eireife,  Befruchtung  u.  Furchungsprozess.  In  Hertwig's  Handbuch  der 
vergleichenden  u.  experimentellen  Entwickelungslehre  der  Wirbeltiere.  Bd.  I,  Teil  I,  1903. 
Also  contains  extensive  bibliography. 

KEIBEL,  F.  and  MALL,  F.  P.:  Manual  of  Human  Embryology.  Vol.  I,  Chap.  VII, 
Philadelphia,  1910. 

KELLICOTT,  W.  E.:  General  Embryology,  1913. 

LONG,  J.  A.  and  MARK,  E.  L.:  The  Maturation  of  the  Mouse  Ovum.  Carnegie  Insti- 
tution, Washington,  D.  C.,  1911. 

MORGAN,  T.  H.:  Heredity  and  Sex,  1913. 

SOBOTTA,  J.:  Die  Befruchtung  und  Furchung  des  EiesderMaus.  Archiv  f.  mik.  Anato- 
mie;  Bd.  XLV,  1895. 

SOBOTTA,  J.:  Ueber  die  Bildung  des  Corpus  luteum  beim  Meerschweinchen.  Anal. 
Hefte,  Bd.  XXXII,  Heft  XCVI,  1906. 

VON  LENHOSSEK,  M.:  Untersuchungen  liber  Spermatogenese.  Archiv  f.  mik.  Anatomie, 
Bd.  LI,  1898. 

WILLIAMS,  J.  W.:  Text-book  of  Obstetrics.     New  York,  1903. 

WILSON,  E.  B.:  The  Cell  in  Development  and  Inheritance.     2d  Ed.,  1900. 

WILSON,  E.  B. :  Observation  on  the  Maturation  Phenomena  in  Certain  Hemiptera.  Jour, 
of  Exper.  Zool.,  Vol.  13,  1912. 


CHAPTER  IV. 
FERTILIZATION. 

When  the  complex  maturation  processes  described  in  the  preceding  chapter 
are  completed,  the  spermatozoon  is  ready  for  union  with  the  mature  ovum. 
This  union,  which  forms  the  starting  point  of  a  new  individual  in  all  sexual 
reproduction,  is  known  as  fertilization,  and  the  resulting  cell  is  the  fertilized 
oi'iim. 

The  details  of  the  process  vary  in  different  animals.  Its  essence  is  the 
entrance  of  the  spermatozoon  into  the  ovum  and  the  union  of  the  nucleus  of 
the  spermatozoon  with  the  nucleus  of  the  ovum.  At  the  time  of  its  entrance 
into  the  egg,  the  sperm  head  is  small  and  its  chromatin  extremely  condensed 
(Fig.  22,  2).  Soon  after  entering  the  ovum,  however,  the  sperm  head  under- 
goes development  into  a  typical  nucleus,  the  male  pronudeus  (Figs.  22,  3,  and 
13,  C).  This  male  pronucleus  is  to  all  appearances  exactly  similar  in  structure 
to  the  nucleus  of  the  egg,  which  latter  is  now  known  as  the  female  pronucleus. 
The  chromatin  networks  in  both  pronuclei  next  pass  into  the  spireme  stage,  the 
spiremes  segmenting  into  chromosomes  of  which  each  pronucleus  contains  one- 
half  the  somatic  number.  The  nuclear  membranes  meanwhile  disappear  and 
the  chromosomes  lie  free  in  the  cytoplasm.  During  these  changes  in  the  pro- 
nuclei,  the  amphiaster  has  formed  and  the  male  and  the  female  chromosomes 
mingle  in  its  equatorial  plane  (Fig.  22,  5).  At  this  stage  no  actual  differentia- 
tion can  be  made  between  male  chromosomes  and  female  chromosomes,  the 
differentiation  shown  in  Fig.  22,  5,  being  schematic.  The  picture  is  now  that 
of  the  end  of  the  prophase  of  ordinary  mitosis,  the  somatic  number  of  chromo- 
somes being  arranged  in  a  plane  midway  between  the  two  centrosomes.  With 
the  mingling  of  male  and  female  chromosomes  fertilization  proper  comes  to  an 
end.  The  further  steps  are  also  identical  with  those  of  ordinary  mitosis.  Each 
chromosome  splits  longitudinally  into  two  exactly  similar  parts  (Fig.  22,  5), 
one  of  which  is  contributed  to  each  daughter  nucleus  (Fig.  22,  6),  and  the  cell 
body  divides  into  two  equal  parts.  (For  details  of  succeeding  anaphase  and 
telophase  see  p.  6.)  There  thus  result  from  the  first  division  of  the  fertilized 
ovum,  two  cells  which  are  apparently  exactly  alike  and  each  of  which  contains 
exactly  the  same  amount  of  male  and  of  female  chromosome  elements  (Fig.  22,  6). 

The  amphiaster  of  the  fertilized  ovum  appears  to  develop  as  in  ordinary 
mitosis.  As  to  the  origin  of  the  centrosomes,  however,  much  uncertainty  still 

33 


34 


TEXT-BOOK   OF   EMBRYOLOGY. 


exists.  The  middle  piece  of  the  spermatozoon  always  enters  the  ovum  with  the 
head.  It  has  already  been  shown  (p.  24)  that  one  or  two  spermatid  centro- 
somes  take  part  in  the  formation  of  the  middle  piece.  Male  centrosome  ele- 
ments are  therefore  undoubtedly  carried  into  the  ovum  in  the  middle  piece.  It 


Zona  pellucida 

Nucleus 
^••7=^"  Spermatozoon 


Female 
s*  pronucleus 


Head  of 

—  spermatozoon 
with  centrosome 


Female  pronucleus 


Male  pronucleus 


.  Chromosomes  of 
female  pronucleus 


*^  Chromosomes  of 
male  pronucleus 


"Centrosome 


Centrosome 


Male  pronucleus 
Female  pronucleus 


Chromosome  from 
female  pronucleus 


rr"I^^  Chromosome  from 
/        male  pronucleus 


Centrosome 


FIG.   22. — Diagram  of  fertilization  of  the  ovum.     (The  somatic  number   of   chromosomes    is   4.) 

Boveri,  Bohm  and  von  Davidoff. 

is  equally  well  known,  for  some  forms  at  least,  that  the  centrosome  of  the  ovum 
disappears  just  after  the  extrusion  of  the  second  polar  body.  In  a  considerable 
number  of  forms  the  development  of  the  centrosome  of  the  fertilized  egg  from, 
or  in  close  relation  to  the  middle  piece  of  the  spermatozoon  has  been  observed. 
The  details  of  the  process  as  it  occurs  in  the  sea-urchin  have  been  carefully 


FERTILIZATION. 


35 


described  by  Wilson.     In  cases  of  this  type  the  tail  of  the  spermatozoon  re- 
mains outside  the  egg  while  the  head  and  middle  piece,  almost  immediately 


FIG.  23.— Fertilization  of  the  ovum  of  Thalassema.    Griffin. 
^ ,  Male  pronucleus,    **,  female  pronucleus. 

after  entering,  turn  completely  around  so  that  the  head  points  away  from  the 
female  pronucleus  (Fig.  23,  a).  An  aster  with  its  centrosomes  next  appears, 
developing  from,  or  in  very  close  relation  to  the  middle  piece.  The  aster  and 


36  TEXT-BOOK   OF   EMBRYOLOGY. 

sperm  nucleus  now  approach  the  female  pronucleus,  the  aster  leading  and  its 
rays  rapidly  extending.  On  or  before  reaching  the  female  pronucleus  the  aster 
divides  into  two  daughter  asters  (Fig.  23,  b)  which  separate  with  the  formation 
of  the  usual  central  spindle,  while  the  two  pronuclei  unite  in  the  equatorial 
plane  and  give  rise  to  the  chromosomes  of  the  cleavage  nucleus  (Fig.  23,  c  and 
d).  In  the  sea-urchin  the  polar  bodies  are  extruded  before  the  entrance  of  the 
spermatozoon.  In  cases  where  the  polar  bodies  are  not  extruded  until  after 
the  entrance  of  the  spermatozoon  (Ascaris,  Fig.  14)  the  amphiaster  forms  while 
waiting  for  their  extrusion,  the  nuclei  joining  subsequently.  When  the  sperm 
head  finds  the  polar  bodies  already  extruded,  union  of  the  two  pronuclei  may 
take  place  first,  followed  by  division  of  the  centrosome  and  the  formation  of  the 
amphiaster. 

The  coming  together  of  ovum  and  spermatozoon  is  apparently  determined 
in  some  cases  by  a  definite  attraction  on  the  part  of  the  ovum  toward  the  sperma- 
tozoon. This  attraction  seems  to  be  of  a  chemical  nature,  but  is  often  not  lim- 
ited to  the  attraction  of  spermatozoa  of  the  same  species.  Foreign  spermatozoa 
will  be  attracted  and  will  enter  the  ovum  if  they  are  physically  able  to  do  so. 
The  entrance  of  these  spermatozoa  may  even  start  the  process  of  cleavage, 
though  such  cleavage  is  usually  abnormal  and  does  not  progress  very  far.  That 
this  attraction  is  not  dependent  upon  the  integrity  of  the  ovum  as  an  organism 
is  shown  by  the  fact  that  small  pieces  of  egg  cytoplasm  free  from  nuclear  ele- 
ments exert  the  same  attractive  force,  so  that  spermatozoa  are  not  only  attracted 
to  them,  but  will  actually  enter  them.  In  other  cases  the  stimulus  for  fertiliza- 
tion is  obviously  one  of  contact.  The  spermatozoa  of  some  Fishes  will  swim 
around  at  random  until  they  touch  any  object  when  they  become  attached  and 
are  unable  to  escape.  Fertilization  in  these  cases  is  therefore  a  matter  of  chance 
favored  by  the  enormous  number  of  sperms  produced,  and  by  the  special  breed- 
ing habits  which  insure  a  close  proximity  of  sperms  and  eggs. 

Of  eggs  which  are  enclosed  by  a  distinct  membrane,  the  vitelline  membrane, 
some  (e.g.,  those  of  Amphibians  and  of  Mammals)  are  permeable  to  the  sper- 
matozoon at  all  points;  others  have  a  definite  point  at  which  the  spermatozoon 
must  enter,  this  being  of  the  nature  of  a  channel  through  the  membrane — the 
micropyle.  In  some  instances  a  little  cone-shaped  projection  from  the  surface 
of  the  egg,  the  attraction  cone  (Fig.  22,  i),  either  precedes  or  immediately  fol- 
lows the  attachment  of  the  spermatozoon  to  the  egg.  Instead  of  a  projection 
there  may  be  a  depression  at  the  point  of  entrance. 

There  seems  to  be  no  question  that  but  one  spermatozoon  has  to  do  with 
the  fertilization  of  a  particular  ovum.  In  Mammals  only  one  spermatozoon 
normally  pierces  the  vitelline  membrane  although  several  may  penetrate  the 
zona  pellucida  (Fig.  22,  i)  to  the  peri  vitelline  space.  Should  more  than  one 
spermatozoon  enter  such  an  egg — as,  for  example,  in  pathological  polyspermy— 


FERTILIZATION. 


37 


the  result  is  an  irregular  formation  of  asters  and  polyasters  (Fig.  24)  and  the 
early  death  of  the  egg  either  before  or  soon  after  a  few  attempts  at  cleavage. 
In  some  Insects,  and  in  Selachians,  Reptiles  and  Birds,  a  number  of  sperma- 
tozoa normally  enter  an  ovum,  but  only  one  goes  on  to  form  a  male  pronucleus. 
The  ovum  thus  not  only  exerts  an  attractive  influence  toward  spermatozoa, 
but  it  apparently  exerts  this  influence  only  until  the  one  requisite  to  its  fertiliza- 
tion has  entered,  after  which  it  appears  able  to  protect  itself  against  the  further 
entrance  of  male  elements.  As  to  the  means  by  which  this  is  accomplished 
little  is  known,  although  several  theories  have  been  advanced.  It  may  be  that 
when  the  single  spermatozoon  necessary  to  accomplish  fertilization  has  entered 
the  ovum,  it  sets  up  within  the  ovum  such  changes  as  to  destroy  the  attractive 


FIG.  24. — Polyspermy  in  sea-urchin  eggs  treated  with  0.005  Per  cent.  nicotine  solution.     O.  and  R. 

Hertwig,  Wilson. 

B,  Showing  ten  sperm  nuclei,  three  of  which  have  conjugated  with  female  pronucleus.     C,  Later 
stage  showing  polyasters  formed  by  union  of  sperm  amphiasters. 

powers  of  the  ovum  toward  other  spermatozoa,  or  as  even  to  prevent  their 
entrance.  In  the  case  of  eggs  where  the  spermatozoon  enters  through  a  micro- 
pyle,  it  has  been  suggested  that  the  tail  of  the  first  spermatozoon  remaining  in 
the  opening  might  effectually  block  the  entrance  to  other  spermatozoa;  or  the 
passage  of  the  first  spermatozoon  might  set  up  such  mechanical  or  chemical 
changes  in  the  canal  as  would  prevent  further  access.  In  most  cases  of  eggs 
which  have  no  vitelline  membrane  previous  to  fertilization,  such  a  membrane 
is  formed  immediately  after  the  entrance  of  the  first  spermatozoon,  a  natural 
inference  being  that  this  membrane  may  prevent  the  entrance  of  any  more 
spermatozoa.  Biologists,  however,  are  inclined  to  discredit  the  view  that  the 
fertilization  membrane  is  a  protection  against  polyspermy. 

Nothing  is  known  in  regard  to  fertilization  of  the  human  ovum.  It  has  been 
shown  that  in  some  of  the  lower  Mammals  fertilization  regularly  takes  place 
in  the  oviduct,  and  it  is  reasonable  to  assume  that  it  occurs  in  the  oviduct  in 
man.  That  spermatozoa  can  pass  into  and  even  all  the  way  through  the  ovi- 


38  TEXT-BOOK  OF   EMBRYOLOGY. 

duct  is  proved  by  cases  of  tubal,  abdominal  and,  rarely,  ovarian  pregnancies. 
On  the  other  hand  Wyder  considers  the  uterus  as  the  normal  site  of  fertiliza- 
tion, and  some  other  gynecologists  say  that  fertilization  may  take  place  in  the 
uterus.  Waldeyer  also  concludes  that  fertilization  may  occur  in  the  uterus. 

Significance  of  Fertilization. 

The  meaning  of  such  a  widely  occurring  phenomenon  as  fertilization  has 
been  interpreted  differently  by  different  scientists,  and  the  question  is  still  far 
from  definite  solution.  Its  chief  importance  must  be  considered  probably  from 
a  standpoint  of  inheritance  and  is  intimately  associated  with  the  interpretation 
of  the  maturation  processes  of  the  germ  cells  (p.  25).  There  are,  however, 
several  views  which  may  be  briefly  mentioned. 

The  earlier  belief  that  fertilization  was  a  necessary  antecedent  to  cleavage 
of  the  ovum  has  been  destroyed  by  the  evidence  of  recent  years.  Loeb  and 
others  have  been  able  to  induce  artificial  parthenogenesis  in  forms  reproducing 
normally  by  sexual  reproduction.  Thus  cleavage  has  been  started  by  chemical 
stimulation  in  the  eggs  of  many  Molluscs,  Echinoderms,  Coelenterates,  and 
even  in  some  of  the  lower  Chordates  (Teleosts  and  Amphibians).  By  fertilizing 
pieces  of  egg-cytoplasm  containing  no  nuclear  material,  parthenogenesis  of  the 
sperm  has  likewise  been  produced.  While  cleavage  produced  in  this  manner 
progresses  only  a  short  way,  the  evidence  points  to  the  conclusion  that  fertiliza- 
tion is  not  an  absolutely  necessary  factor  in  reproduction,  although  it  normally 
occurs  in  the  great  majority  of  cases. 

Another  view,  advocated  by  Richard  Hertwig  and  others,  is  that  fertilization 
induces  a  rejuvenescence  of  protoplasm.  According  to  this  view  protoplasm 
gradually  passes  into  a  state  of  senescence  in  which  its  activity  is  diminished. 
With  the  admixture  of  new  protoplasm  during  fertilization  a  new  period  of 
vigorous  activity  is  initiated.  The  life  cycles  of  certain  Protozoa  are  brought 
to  the  support  of  this  hypothesis.  In  these  Protozoa  a  long  period  of  reproduc- 
tion by  a  series  of  cell  divisions  is  followed  by  some  form  of  conjugation.  Two 
individuals  come  together  and  an  exchange  of  nuclear  material  takes  place. 
As  a  result  a  new  impetus  is  given  to  the  protoplasmic  activity,  and  each  of  the 
conjugants  starts  again  on  a  long  period  of  reproduction.  It  is  highly  probable 
that  the  admixture  of  new  protoplasm  in  fertilization  among  Metazoa  produces 
a  similar  invigorating  effect. 

Another  interpretation  of  fertilization  is  that  of  Weissman  who  believed 
that  fertilization  or  "amphimixis"  is  important  as  a  source  of  variation.  Since 
the  chromatin  of  different  individuals  varies  more  or  less,  fertilization  will  pro- 
duce new  combinations  and  tend  to  the  production  of  new  forms.  However, 
there  is  very  little  evidence  that  forms  which  reproduce  sexually  show  more 
variations  than  those  reproducing  by  parthenogenesis. 


FERTILIZATION.  39 

References  for  Further  Study. 

COXKLIN,  E.  G.:  The  Embryology  of  Crepidula.     Jour,  of  Morphol.,  Vol.  XIII,  1897. 

HARTMAN,  C.  G.:  Studies  in  the  Development  of  the  Opossum.  Jour,  of  M  or  ph.,  Vol. 
XXVII,  No.  i,  1916. 

HARPER,  E.  H.:  The  Fertilization  and  Early  Development  of  the  Pigeon's  Egg.  Am. 
Jour,  of  Anat.,  Vol.  Ill,  No.  4,  1904. 

HERTWIG,  R.:  Eireife,  Befruchtung  u.  Furchungsprozess.  In  Hertwig's  Handbuch  d. 
I'ergleich.  u.  experiment.  Eniwickelungslehre  der  Wirbeltiere,  Bd.  I,  Teil  I,  1903. 

HUBER,  G.  CARL:  The  Development  of  the  Albino  Rat.  Memoirs  of  the  Wistar  Insti- 
tute, No.  5,  Philadelphia,  1915. 

KELLICOTT,  W.  E.:  General  Embryology.     New  York,  1913. 

KING,  H.  D.:  The  Maturation  and  Fertilization  of  the  Egg  of  Bufo  lentiginosus.  Jour. 
of  Morphol.,  Vol.  XVII,  1901. 

LOEB,  J.:  Die  Chemische  Entwicklungserregung  des  Thierischen  Eies.     Berlin,  1909. 

SOBOTTA,  J.:  Die  Befruchtung  u.  Furchung  des  Eies  der  Maus.  Arch.  f.  mik.  Anal., 
Bd.  XLV,  1895. 

WILSON,  E.  B.:  The  Cell  in  Development  and  Inheritance.     2d  Ed.,  1900. 


CHAPTER  V. 


CLEAVAGE— (SEGMENTATION) . 

Following  fertilization  and  the  commingling  of  male  and  female  chromo- 
somes, there  occurs  the  usual  longitudinal  splitting  of  these  chromosomes  as  in 
ordinary  mitosis.  One-half  of  each  chromosome  now  passes  toward  each 
centrosome.  The  result  is  that  one-half  of  each  male  chromosome  and  one- 
half  of  each  female  chromosome  enter  into  the  formation  of  each  of  the  two 
new  daughter  nuclei  (Fig.  22,  4,  5  and  6).  The  phenomena  which  follow  are 
apparently  identical  with  those  of  ordinary  mitosis  and  result  in  two  similar 
daughter  cells.  Each  of  the  latter  next  undergoes  mitotic  division.  In  this 
manner  are  formed  four  cells,  eight  cells,  sixteen  cells,  and  so  on.  This  early 
multiplication  of  cells  which  follows  fertilization  is  known  as  cleavage  or  seg- 
mentation of  the  ovum,  the  cells  themselves  are  known  as  Uastomeres  and  the 
cell  mass  as  ihe^momla. 

Important  differences  occur  in  the  cleavage  of  eggs  of  different  forms  of 
animals,  due  in  large  measure  to  the  mechanical  factors  incident  to  variations 
in  the  amount  of  yolk  and  its  distribution  within  the  egg.  Upon  this  basis  the 
following  classification  of  the  forms  of  cleavage  has  been  made. 

FORMS  OF  CLEAVAGE. 

a.  Equal — e.g.,     meiolecithal     eggs     of 

Sponges,  Echinoderms,  some 
Annelids,  some  Crustaceans, 
some  Mollusks,  Amphioxus, 
Mammals. 

b.  Unequal — e.g.,  mesolecithal   eggs   of 

Cyclostomes,  Ganoid  Fishes, 
Ainphibians;  usual  type  in 
Annelids  and  Mollusks. 

a.  Superficial — e.g.,    centrolecithal    eggs 

of  Arthropods. 

b.  Discoidal — e.g.,  polylecithal   eggs   of 

Cephalopods,     Bony    Fishes, 
Reptiles,  Birds. 
40 


Holoblastic  (complete  or  total) 


Meroblastic  (incomplete  or  partial) 


CLEAVAGE. 


41 


Holoblastic  Cleavage. 


(A)  EQUAL. — In  this  form  of  cleavage  the  entire  egg  divides  and  the  cells 
resulting  from  the  early  cell  divisions  are  of  approximately  the  same  size.  One 
of  the  Echinoderms — Synapta — presents  a  beautiful  example  of  this,  the  sim- 
plest type  of  cleavage  (Fig.  25).  The  egg  of  synapta  is  meiolecithal,  contain- 
ing very  little  yolk.  The  first  cleavage  is  in  a  vertical  plane  at  right  angles  to  the 
long  axis  of  the  central  spindle  and  divides  the  egg  into  halves.  The  second 
plane  of  cleavage  is  also  vertical  but  is  at  right  angles  to  the  first  cleavage  plane 
and  results  in  four  equal  cells.  The  third  cleavage  plane  is  horizontal,  cutting 
the  four  cells  resulting  from  the  second  cleavage  into  eight  equal  cells.  The 
fourth  cleavage  is  vertical,  the  fifth  horizontal  and  so  on,  regular  alternation  of 


FIG.  25. — Cleavage  of  the  ovum  of  Synapta   (slightly  schematized).    Selenka,   Wilson. 
A-E,  Successive  cleavages  to  the  32-cell  stage.     F,  Blastula  of  128  cells. 


vertical  and  horizontal  cleavage  planes  being  continued  through  the  ninth  set 
of  divisions,  resulting  in  512  cells.  At  this  point  gastrulation  begins  and  the 
regularity  of  the  cleavage  planes  is  lost.  Amphioxus  is  another  classical  ex- 
ample of  equal  holoblastic  cleavage,  being  classed  as  such,  although  after  the 
third  cleavage  the  cells  are  not  of  exactly  the  same  size.  In  Amphioxus  the 
first  two  cleavage  planes  are  vertical  and  at  right  angles,  as  in  Synapta.  The 
third  cleavage  plane  is  horizontal,  as  in  Synapta,  but  the  cells  lying  above  the 
third  cleavage  plane  are  smaller  than  those  lying  below  it.  The  eight-cell  stage 


42  TEXT-BOOK   OF  EMBRYOLOGY. 

of  Amphioxus  thus  presents  four  upper  smaller  cells  and  four  lower  larger 
cells  (Fig.  26). 

The  difference  in  size  between  the  four  upper  and  the  four  lower  blastomeres 
in  Amphioxus  finds  probable  explanation  in  the  distribution  of  yolk  within  the 
egg  and  the  first  four  blastomeres.  The  yolk  is  greater  in  amount  at  the  lower 
pole  of  the  cell,  thus  leaving  the  greater  amount  of  protoplasm  at  the  upper 
pole.  The  nucleus  tends  to  occupy  the  center  of  the  protoplasmic  mass  and 
consequently  is  nearer  the  upper  pole.  Therefore  when  the  spindle  forms 
about  the  nucleus,  the  plane  bisecting  the  spindle  at  right  angles  will  be  nearer 
the  upper  pole  of  the  cell.  This  plane  corresponding  to  the  division  plane 
of  mitosis,  the  two  resulting  cells  will  be  unequal  in  size,  the  smaller  one 


Micromeres 

Segmentation 
cavity 


Macromeres 


FIG.  26. — Cleavage  of  the  ovum  of  Amphioxus.     Hatschek,  Bonnet. 
1-5,  Lateral  views  of  segmenting  cells;  6,  section  of  blastula. 

lying  above  and  the  larger  below.     Thus  is  shown  one  of  the  effects  of  yolk 
distribution. 

(B)  UNEQUAL. — A  good  example  of  this  form  of  cleavage  is  found  in  the 
common  frog's  egg  (Fig.  27).  This  egg  while  containing  little  yolk  when  com- 
pared with  such  eggs  as  those  of  the  fowl,  contains  much  more  yolk  than  does 
the  egg  of  Synapta  or  of  Amphioxus.  The  frog's  egg  being  a  telolecithal  egg, 
the  yolk  is  gathered  at  one  pole,  enabling  a  distinct  differentiation  to  be  made 
between  the  upper  darker  protoplasmic  or  animal  pole,  and  the  lower  lighter 
vegetative  pole  (Fig.  6).  The  cleavage  is  complete  but  the  cells  which  develop 
at  the  yolk  pole  are  much  larger  than  those  which  develop  at  the  protoplasmic 
pole.  The  first  and  second  cleavage  planes  are  as  in  Synapta  and  Amphioxus, 
vertical  and  at  right  angles  to  each  other.  Each  of  the  four  cells  which  result 
from  the  second  cleavage  in  the  frog  consists  of  a  small  upper  darker  protoplas- 
mic pole  and  of  a  larger  lower  lighter  yolk  pole  (Fig.  27,  A).  The  nuclear 


CLEAVAGE. 


43 


elements  lying,  as  they  always  do,  within  the  protoplasmic  portion  of  the  cell, 
determine  the  next  cleavage  plane  which  is  horizontal  and  lies  nearer  the  proto- 
plasmic ends  of  the  cells.  The  result  is  that  the  third  cleavage  gives  rise  to 
eight  cells,  four  of  which  are  small  protoplasmic  cells  lying  above  the  line  of 
cleavage,  while  the  other  four  are  large  yolk-containing  cells  which  lie  below 
the  line  of  cleavage  (Fig.  27,  A).  This  distinction  between  protoplasmic  cells 


B 


D 


H 


I 


FIG.  27. — Cleavage  of  the  frog's  egg.     Morgan. 

A,  Eight-cell  stage;  B,  beginning  of  sixteen-cell  stage;  C,  thirty-two-cell  stage;  D,  forty-eight-cell 
stage  (more  regular  than  usual);  E,  F,  G,  later  stages;  H,  I,  formation  of  blastopore. 

and  yolk  cells  not  only  persists  but  tends  to  become  more  and  more  marked  as 
segmentation  proceeds,  and  it  soon  becomes  evident  that  the  cells  unencum- 
bered by  yolk  have  a  tendency  to  segment  more  rapidly  than  do  their  yolk- 
laden  brethren  (Fig.  27,  C,  D,  E,  F  and  G).  Thus,  while  the  fourth  cleavage 
is  vertical  in  both  types  of  cells,  giving  rise  to  eight  upper  protoplasmic  cells 
and  the  same  number  of  lower  yolk  cells,  this  uniformity  of  number  persists 


44 


TEXT-BOOK  OF   EMBRYOLOGY. 


only  up  to  this  point,  while  beyond  this  point  the  protoplasmic  cells  increase  in 
number  much  more  rapidly  than  do  the  yolk  cells,  so  that  when  the  protoplasmic 
cells  number  128,  there  are  still  but  comparatively  few  yolk  cells.  There  thus 
result  in  total  unequal  cleavage,  cells  of  two  very  different  sizes  each  confined 
to  its  own  part  of  the  segmenting  cell  mass. 


Meroblastic  Cleavage. 

(A)  SUPERFICIAL. — This  form  of  cleavage  is  seen  in  the  centrolecithal  eggs 
of  Arthropods.     These  eggs  consist  of  a  central  mass  of  nutritive  yolk  sur- 


c  d 

FIG.  28. — Cleavage  in  hen's  egg.     Coste.     Germinal  disk  and  part  of    yolk,  seen  from  above. 

rounded  by  a  comparatively  thin  layer  of  protoplasm.  The  segmentation 
nucleus  lies  in  the  middle  of  the  nutritive  yolk  where  it  undergoes  the  usual 
mitotic  divisions.  The  resulting  daughter  nuclei  leave  the  central  yolk  mass 
and  pass  out  into  the  peripheral  layer  of  protoplasm  where  they  apparently 


CLEAVAGE.  45 

determine  segmentation  of  the  protoplasm,  the  number  of  protoplasmic  seg- 
ments corresponding  to  the  number  of  nuclei.  There  is  thus  formed  a  super- 
ficial layer  of  cells  (blastomeres)  enclosing  the  central  nutritive  yolk. 

(B)  DISCOIDAL. — This  type  of  cleavage  occurs  in  eggs  which  have  an  ex- 
cessive amount  of  yolk  and  in  which  the  protoplasm  is  confined  to  a  small  super- 
ficial germ  disk.  The  telolecithal  ova  of  Birds  furnish  typical  examples  of  this 
form  of  cleavage.  The  first  cleavage  plane  is  vertical  and  divides  the  proto- 
plasmic disk  into  halves.  The  second  cleavage  plane  is  also  vertical  and  at 
right  angles  to  the  first,  resulting  in  four  approximately  equal  cells  (Fig.  28,  a). 
The  third  cleavage  plane  is  also  vertical,  dividing  two  of  the  four  cells  (Fig.  28, 
b).  The  germ  disk  at  the  end  of  the  third  cleavage  consists  of  six  pyramidal 
cells  lying  with  their  apices  together  in  the  center  of  the  germ  disk,  their  bases 
lying  peripherally  and  toward  the  yolk  mass.  They  are  separated  from  one 
another  at  the  surface,  but  are  still  continuous  below  and  peripherally  with  the 

y.s.  g.a.      s.c.         w.y. 


FIG.  29.— From  a  vertical  section  through  the  germ  disk  of  a  fresh-laid  hen's  egg.     Duval,  Herturig. 
g.d.,  Upper  layer  of  germ  disk;  s.c.,  segmentation  cavity;  w.y.,  white  yolk  (see  Fig.  7);  y.s.,  lower 
layer  of  germ  disk  (yolk  cells,  merocytes). 

underlying  yolk  mass  and  consequently  with  each  other.  The  analogy  be- 
tween this  condition  and  that  described  for  the  frog's  egg  is  complete  with  the 
one  exception  that  in  the  latter  the  cleavage  furrows  cut  completely  through 
the  yolk  cells  or  the  yolk-containing  portions  of  the  cells,  while  in  the  bird's  egg 
the  amount  of  yolk  is  so  great  that  the  cleavage  furrow  merely  passes  a  short 
distance  into  it  without  completely  dividing  it  into  segments.  The  fourth 
cleavage  plane  is  tangential,  cutting  off  the  apices  of  the  six  pyramidal  segments. 
The  germ  disk  after  the  fourth  cleavage  thus  consists  of  six  small  superficial 
central  cells  and  six  larger  cells  which  surround  the  small  cells  and  also  separate 
the  latter  from  the  underlying  yolk.  From  this  point  radial  and  tangential 
cleavages  follow  each  other  without  any  semblance  of  regularity.  The  result 
is  a  mass  of  small  cells  lying  at  the  center  of  the  disk  and  surrounded  by  larger 
cells  (Fig.  28,  c,  d).  The  smaller  cells  are  completely  separated  from  the  under- 
lying yolk  while  the  larger  cells  are  for  a  time  continuous  with  it  (Fig.  29). 
Comparing  the  unequal  holoblastic  cleavage  of  the  frog's  egg  with  discoidal 


46  TEXT-BOOK  OF   EMBRYOLOGY. 

meroblastic  cleavage  as  seen  in  the  eggs  of  Birds,  it  becomes  immediately  evi- 
dent that  the  differences  between  them  are  explainable  entirely  by  reference  to 
the  greater  quantity  of  yolk  in  the  bird's  egg.  The  real  activity  of  segmenta- 
tion is  in  both  cases  confined  almost  wholly  to  the  protoplasm.  In  the  frog's 
egg  the  amount  of  yolk  present  is  sufficient  to  impede  segmentation  in  the 
larger  cells  but  not  to  prevent  it.  In  the  bird's  egg  the  amount  of  yolk  is  so 
great  that  it  cannot  be  made  to  undergo  complete  segmentation. 

Reviewing  the  results  of  cleavage,  it  is  to  be  noted  that  in  every  case  there  is 
formed  a  larger  or  a  smaller  group  of  cells.  In  the  case  of  equal  holoblastic 
cleavage,  these  cells  are  all  of  the  same  or  of  nearly  the  same  size,  and  constitute 

Micromeres. 


mz 


Macromeres. 

FIG.  30. — From  a  sagittal  section  through  blastula  of  frog.     Bonnet, 
mz.,  Marginal  zone. 


what  is  known  as  the  morula  or  mulberry  mass  (Fig.  25,  E).  A  similar  condition 
obtains  in  unequal  holoblastic  cleavage  with  the  one  exception,  that  there  is  a 
marked  difference  in  the  size  of  the  cells  constituting  the  morula  (Fig.  27).  In 
superficial  meroblastic  cleavage  the  group  of  cells  forms  a  layer  enclosing  the 
central  yolk,  the  latter  being  unsegmented  but  containing  some  nuclei.  In 
discoidal  meroblastic  cleavage  the  group  of  cells  spreads  itself  over  a  limited 
superficial  area,  while  beneath  it  lies  the  large  mass  of  unsegmented  yolk,  con- 
taining, however,  some  nuclei  (Figs.  28  and  29). 

In  holoblastic  cleavage  the  blastomeres  in  the  interior  of  the  mass  become 
more  or  less  separated  during  segmentation,  a  cavity  thus  being  formed  within 
the  so-called  morula.  This  cavity  increases  in  size,  the  cells  being  pushed 
centrifugally,  and  the  embryo  soon  consists  of  a  layer  or  layers  of  cells  enclosing 


CLEAVAGE. 


a  cavity,  the  segmentation  cavity.  The  entire  embryo  is  now  known  as  the 
blastula. 

The  simplest  type  of  blastula  is  seen  in  Amphioxus,  where  it  consists  of  a 
nearly  spherical  segmentation  cavity  surrounded  by  a  single  layer  of  cells. 
Some  of  the  cells — those  which  are  more  ventral  and  contain  the  larger  amount 
of  yolk — are  slightly  larger  than  others  (Fig.  26,  6). 

In  the  eggs  of  the  frog,  in  which  the  cells  resulting  from  segmentation  show 
greater  inequality  in  size  (due  to  difference  in  yolk  content),  the  segmentation 
cavity  is  surrounded  by  several  layers  of  cells.  In  such  a  blastula  the  roof  of 
the  cavity  is  comparatively  thin,  being  composed  of  small  cells  containing  little 
yolk,  micromeres,  while  the  floor  of  the  cavity  is  thick,  being  composed  of  large 


FIG.  31. — Four  stages  in  cleavage  of  the  ovum  of  the  mouse.    Sobotta 
Small  cell  marked  with  x  is  the  polar  body. 

•:olk  cells,  macromeres.  So  thick  is  this  wall  of  the  vegetative  pole  of  the  blastula 
that  the  large  yolk  cells  extend  into  the  segmentation  cavity  compressing  it  into 
a  crescentic  cleft  (Fig.  30).  In  the  frog  the  roof  of  the  segmentation  cavity  is 
sharply  denned  from  the  floor,  due  to  the  fact  that  the  outer  layer  of  cuboidal 
roof  cells  is  densely  pigmented.  The  rather  sharply  defined  zone  of  transition 
between  pigmented  micromeres  and  nonpigmented  macromeres  is  known  as  the 
marginal  zone. 

In  discoidal  segmentation,  the  segmentation  cavity  is  a  mere  slit  between  the 
superficial  protoplasmic  cells  and  the  underlying  unsegmenting  yolk  with  its 
yolk  nuclei  (Fig.  29).  Comparing  it  with  unequal  holoblastic  cleavage,  these 
partially  divided  yolk  cells  which  form  the  floor  of  the  segmentation  cleft  in 
discoidal  cleavage  are  analogous  to  the  large  yolk  cells  which  form  the  floor  of 
the  segmentation  cavity  in  the  frog.  (Compare  Figs.  29  and  30.) 


48 


TEXT-BOOK   OF   EMBRYOLOGY. 


In  the  mammalian  ovum,  as  in  the  other  cases  just  described,  segmentation 
leads  up  to  the  formation  of  a  solid  mass  of  cells — the  morula.  While  cleavage 
here  is  of  the  holoblastic  equal  type,  the  irregularity  is  especially  marked.  In 
the  mouse,  for  example,  the  second  cleavage  is  complete  in  one  of  the  blasto- 
meres  before  it  has  begun  in  the  other,  so  that  a  three-celled  stage  results 
(Fig.  31).  Following  this  is  a  four-celled  stage.  From  this  time  on  cleavage 
continues  irregularly  until  a  solid  mass  is  formed,  as  in  the  lower  forms,  which 
is  composed  of  apparently  similar  cells  (Fig.  32). 

The  next  step  in  mammalian  development  is  a  differentiation  of  the  super- 
ficial layer  of  the  cells  of  the  morula.  The  result,  then,  is  a  single  surface  layer, 
the  covering  layer,  surrounding  a  central  mass  of  polygonal  cells  (Fig.  33,  a). 
This  solid  mass  of  cells  is  transformed  into  a  vesicle  by  vacuolization  of  some  of 


Subzonal 

space 

Morula 


FIG.  32. — Morula  of  rabbit,     van  Beneden. 

the  inner  cells  (Fig.  33)  and  the  confluence  of  these  vacuoles  to  form  a  cavity. 
The  mammalian  ovum  at  this  stage  thus  consists  of  two  groups  of  cells  and  a 
cavity,  an  outer  group  or  layer  of  cuboidal  cells,  the  outer  cell  layer  or  covering 
layer  (trophoderm),  forming  the  wall  of  the  cavity,  and  an  inner  group  of  poly- 
gonal or  spheroidal  cells,  the  inner  cell  mass  which  at  one  point  is  attached  to 
the  outer  layer  of  cells  (Fig.  33,  d). 

The  mistake  must  not,  however,  be  made  of  considering  the  mammalian 
ovum  at  this  stage  as  a  true  blastula.  The  mammalian  ovum  apparently  does 
not  pass  through  any  true  blastula  stage.  Of  the  parts  just  described,  the  inner 
cell  mass  alone  is  comparable  to  the  blastoderm  of  birds,  while  the  cavity  cor- 
responds not  to  the  segmentation  cavity  but  to  the  yolk  mass  of  meroblastic 
eggs.  The  vacuolization  of  the  cells  of  the  inner  cell  mass  would  thus  repre- 
sent a  late  and  abortive  attempt  at  yolk  formation,  the  actual  nutritive  yolk 
being  made  unnecessary,  since  the  attachment  of  the  ovum  to  the  walls  of  the 
uterus  provides  for  direct  parental  nutrition.  In  the  separation  of  the  cells  of 
the  morula  into  an  inner  cell  mass  and  an  outer  covering  layer  is  seen  the  earliest 


CLEAVAGE. 


49 


differentiation  into  cells  (inner  cell  mass),  which  are  destined  to  form  the 
embryo  proper,  and  cells  (outer  cells — covering  layer)  which  are  to  engage  in 
the  development  of  certain  accessory  structures. 

Recent  studies  of  opossum  ova  (Hartman)  have  shown  that  in  this  form  the 
morula  stage  is  absent.  During  segmentation  the  blastomeres  migrate  periph- 
erally and  form  a  single  layer  of  cells  around  a  central  cavity,  although  a  few 
cells  usually  remain  free  within  the  cavity.  At  about  the  4o-celled  stage  the 
majority  of  the  cells  forming  the  wall  of  the  hollow  structure  (blastocyst)  begin 


1 


FIG.  33. — Four  stages  in  the  development  of  the  bat.     van  Beneden. 

a,  Section  of  morula;  b,  section  of  later  stage  of  morula,  showing  differentiation  of  outer  layer  of 
cells;  c,  section  of  still  later  stage,  showing  vacuolization  of  central  cells;  d,  section  showing  outer 
layer  (trophoderm)  and  inner  cell  mass. 

to  diminish  in  thickness,  while  a  few  at  one  point  increase  in  thickness.  The 
latter  proliferate  to  form  a  little  mass  which  probably  corresponds  to  the  inner 
cell  mass  described  for  the  bat.  The  layer  of  thin  cells  forming  the  major 
portion  of  the  wall  of  the  blastocyst  may  be  considered  as  comparable  with  the 
covering  layer  in  the  bat.  The  cells  in  each  region  are  probably  lineal  descend- 
ants of  one  or  the  other  of  the  two  primary  blastomeres,  although  the  latter 
exhibit  no  distinguishing  features;  one  blastomere  gives  rise  to  embryonic 
structures  proper  and  the  other  to  extraembryonic  or  accessory  structures. 


50  TEXT-BOOK   OF  EMBRYOLOGY. 

v 

In  the  albino  rat  (Huber)  cleavage  gives  rise  to  a  true  morula  consisting  of 
from  24  to  32  cells.  Subsequent  to  this  there  appears  among  the  cells  of  the 
morula  a  crescentic  space  which  gradually  enlarges  until  the  cells,  being  pushed 
peripherally,  form  a  relatively  thin  layer  around  a  central  cavity.  At  one  point 
in  the  wall  of  this  hollow  structure  (blastocyst,  blastodermic  vesicle)  a  little 
mass  of  cells  constitutes  the  probable  homologue  of  the  inner  cell  mass  which 
has  been  described  previously. 

References  for  Further  Study. 

ASSHETON,  R.:  The  Segmentation  of  the  Ovum  of  the  Sheep,  with  Observations  on  the 
Hypothesis  of  a  Hypoblastic  Origin  for  the  Trophoblast.  Quart.  Jour,  of  Mic.  Science,  Vol. 
XLI,  1898. 

BLOUNT,  M.:  The  Early  Development  of  the  Pigeon's  Egg,  with  Especial  Reference  to 
the  Supernumerary  Sperm  Nuclei,  the  Periblast  and  the  Germ  Wall.  Biolog.  Bull.,  Vol. 
XIII,  No.  5,  1907. 

CONKLIN,  E.  G.:  Karyokinesis  and  Cytokinesis.  Jour.  Acad.  Nat.  Sci.  of  Philadelphia, 
Vol.  XII,  1902. 

CONKLIN,  E.  G.:  The  Embryology  of  Crepidula.     Jour,  of  MorphoL,  Vol.  XIII,  1897. 

EYCLESHYMER,  A.  C.:  The  Early  Development  of  Amblystoma,  with  Observations  on 
Some  Other  Vertebrates.  Jour,  of  MorphoL,  Vol.  X,  1895. 

HARPER,  E.  H.:  The  Fertilization  and  Early  Development  of  the  Pigeon's  Egg.  Am. 
Jour,  of  Anat.,  Vol.  Ill,  No.  4,  1904. 

HARTMAN,  C.  G.:  Studies  on  the  Development  of  the  Opossum.  Jour,  of  Morph.,  Vol. 
XXVII,  1916. 

HATSCHEK,  B.:  Studien  iiber  Entwickelung  des  Amphioxus.  Arbeiten  aus  dem  zool. 
Instit.  zu  Wien,  Bd.  IV,  1881. 

HERTWIG,  R.:  Eireife,  Befruchtung  u.  Furchungsprozess.  In  Hertwig's  Handbuch  d. 
vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  I,  Teil  I,  1903. 

HUBER,  G.  CARL:  The  Development  of  the  Albino  Rat.  Memoirs  of  the  Wistar  Institute, 
No.  5,  1915. 

LILLIE,  F.  R.:  The  Development  of  the  Chick.     New  York,  1908. 

MORGAN,  T.  H.:  The  Development  of  the  Frog's  Egg.     New  York,  1897. 

SOBOTTA,  J.:  Die  Befruchtung  u.  Furchung  des  Eies  der  Maus.  Arch.  f.  mik.  Anat., 
Bd.  XLV,  1895. 

VAN  BENEDEN,  E.:  Recherches  sur  les  premiers  stades  du  developpement  du  Murin 
(Vespertilio  murinus).  Anat.  Anz.,  Bd.  XVI,  1899. 

WILSON,  E.  B.:  The  Cell  in  Development  and  Inheritance.     2d  Ed.,  1900. 


CHAPTER  VI. 

GERM  LAYERS.* 

THE  TWO  PRIMARY  GERM  LAYERS— FORMATION  OF  THE  GASTRULA. 
Gastrulation  in  Amphioxus. 

The  changes  which  immediately  follow  the  formation  of  the  blastula  can  be 
observed  in  their  simplest  form  in  Amphioxus,  where,  it  will  be  remembered, 
the  blastula  is  a  hollow  sphere  the  wall  of  which  consists  of  a  single  layer  of  cells 
which  enclose  the  segmentation  cavity  (Fig.  26,6).  Gastrulation  begins  by  a 
flattening  of  the  ventral  wall  of  the  blastula  (Fig.  34,  A).  This  is  followed  by 
a  folding  in  or  imagination  of  the  yolk  cells  which  form  the  ventral  wall  (Fig. 
34,  B).  These  cells  press  upward  into  the  segmentation  cavity  which  they  soon 
completely  obliterate,  and  come  to  lie  immediately  beneath  and  in  contact  with 
the  smaller  cells  which  had  formed  the  roof  of  the  cavity  (Fig.  34,  C). 

The  gastnda,  as  the  embryo  is  now  called,  thus  consists  of  two  layers  of  cells 
which  lie  in  close  apposition  and  enclose  the  new  cavity,  the  archenteron  (ccelen- 
teron — primitive  gut)  formed  by  the  imagination  (Fig.  34,  C  and  D).  This 
cavity  remains  open  externally,  the  opening  being  known  as  the  blastopore 
(Fig.  34,  C  and  D) .  These  two  layers  of  cells  which  form  the  wall  of  the  gastrula 
are  the  primary  germ  layers.  The  outer  layer  is  known  as  the  ectoderm  or 
epiblastj  the  inner  layer  as  the  entoderm  or  hypoblast.  As  seen  by  reference  to 
Fig.  34,  C  and  D,  the  two  primary  germ  layers  are  directly  continuous  with  each 
other  at  the  blastopore. 

The  most  significant  feature  of  the  transformation  of  the  blastula  into  the 
gastrula  is  that  whereas  in  the  blastula  all  the  cells  are  essentially  similar, 
differing  if  at  all  only  in  the  amount  of  yolk  contained,  in  the  gastrula  two  dis- 
tinct types  of  cells  are  recognizable.  The  cells  of  the  outer  layer  differ  from 
those  of  the  inner  layer  both  structurally  and  functionally.  Thus  in  some  of  the 
lowest  forms  the  gastrula  stage  is  the  adult  stage.  In  such  the  outer  cells  are 
protective,  react  to  external  stimuli,  develop  cilia  which  determine  locomotion, 
etc.  The  inner  cells,  on  the  other  hand,  are  more  especially  concerned  with 
nutrition,  absorbing  food,  and  giving  off  waste  products.  Von  Baer's  apprecia- 

*  For  many  of  the  ideas  contained  in  this  chapter,  especially  the  correlation  of  gastrulation  and 
the  formation  of  the  mesoderm  in  different  forms,  the  writers  are  indebted  to  Bonnet's  excellent  de- 
scription in  his  "Lehrbuch  der  Entwickelungsgeschichte." 

The  homologizing  of  gastrulation  in  the  different  forms  has  been  found  the  most  satisfactory 
method  of  teaching  the  subject.  At  the  same  time  it  must  be  admitted  that  some  of  the  correlations 
are  not  based  on  actual  observations. 

51 


52 


TEXT-BOOK  OF  EMBRYOLOGY. 


tion  of  the  significance  of  this  first  cell  differentiation  is  evidenced  by  the  fact 
that  he  designated  the  two  primary  germ  layers  the  "primitive  organs"  of  the 
body. 

It  should  be  noted  that  with  the  completion  of  gastrulation  certain  important 
landmarks  in  adult  topography  have  been  established.     Thus  the  animal 


Segmentation  cavity 


Micromeres 


Segmentation  cavity 


Macromeres 


Invagination 


C 

Archenteron 


Blastopore 


Anterior  lip  of  blastopore 


Blastopore 

Post,  lip  of 
blastopore 


Ectoderm    Entoderm  Ectoderm  Entoderm 

FIG.  34. — Gastrulation  in  Amphioxus.     Hatschek,  Bonnet. 

(micromere)  pole  is  always  the  dorsum;  the  vegetative  (macromere)  pole 
always  the  ventrum;  the  blastopore,  being  always  caudal,  differentiates  the 
tail  end  from  the  head  end  of  the  embryo. 

Gastrulation  in  Amphibians. 

This  is  modified  as  compared  with  gastrulation  in  Amphioxus  by  the 
presence  of  a  greater  amount  of  yolk.  A  clear  understanding  of  the  modifica- 
tions which  this  increased  yolk  content  causes  in  the  gastrulation  of  Amphibians, 


GERM  LAYERS. 


53 


as  well  as  of  Reptiles  and  Birds,  is  essential  to  a  proper  appreciation  of  the 
process  in  Mammals. 

Recalling  the  amphibian  blastula  (p.  47),  it  will  be  remembered  that  its 
roof  was  formed  of  smaller  protoplasmic  cells  (micromeres)  while  its  floor  con- 
sisted of  a  mass  of  yolk  cells  which  encroached  upon  the  segmentation  cavity 


Micromeres 


Marginal 
zone 

—  Macromeres 


FIG.  35. — Vertical  section  through  b'.astula  of  Triton.     Hertwig. 

(Fig.  30).  The  zone  of  union  between  the  two  kinds  of  cells  is  known  as  the 
marginal  zone.  The  simplest  type  of  amphibian  gastrulation,  and  the  type 
thus  most  easily  compared  with  gastrulation  in  Amphioxus,  is  exemplified  by 
the  water  salamander — Triton  taeniatus.  (Compare  Figs.  34  and  35.) 


Ectoderm 
Entoderm 


Anterior  lip  of  blastopore 

Blastopore 

Posterior  lip  of  blastopore 

Yolk  cells 
(entoderm) 


Segmenta- 
tion cavity 


FIG.  36. — Vertical  section  through  embryo  of  Triton,  showing  beginning  of  gastrulation.     Hertwig. 

In  Triton,  a  slight  groove  or  furrow  appearing  along  a  portion  of  the  marginal 
zone  marks  the  blastopore  and  the  beginning  of  gastrulation.  The  upper  lip 
of  this  groove  is  formed  by  the  smaller  protoplasmic  cells,  the  lowrer  by  the  large 
yolk  cells  (Fig.  36).  The  groove  next  deepens,  the  micromeres  growing  in  at 
the  dorsal  lip  to  form  the  roof  of  the  archenteron,  while  the  yolk  cells  are  carried 


54  TEXT-BOOK  OF  EMBRYOLOGY. 

over  the  ventral  lip  to  form  the  floor.  The  imagination  cleft  which  thus  be- 
comes the  archenteron  is  at  first  small  as  compared  with  the  segmentation  cavity 
but  rapidly  increases  in  size,  until  as  in  Amphioxus,  the  earlier  cavity  is  finally 
completely  obliterated  (Fig.  37).  Coincident  with  the  carrying  of  the  yolk 
cells  into  the  interior  of  the  vesicle  and  the  obliteration  of  the  segmentation 
cavity,  proliferation  of  the  micromeres  carries  them  completely  around  the  yolk 
cells,  so  that  the  entire  surface  of  the  gastrula  is  formed  of  small  cells  (Fig.  37). 
The  amphibian  gastrula  thus  consists  of  a  central  cavity,  the  archenteron, 
communicating  with  the  exterior  by  means  of  a  small  opening,  the  blastopore, 
the  roof  of  the  cavity  being  formed  by  two  or  more  layers  of  small  cells,  the 
floor  by  the  mass  of  large  yolk  cells.  The  outer  layer  of  cells  completely  sur- 
rounds the  yolk  cells  except  at  the  blastopore,  and  constitutes  the  ectoderm 
(Fig.  37).  The  inner  layer  or  entoderm  is  distinct  only  in  the  roof  of  the  cavity. 
Laterally  its  cells  pass  over  without  any  distinct  demarcation  into  the  mass  of 

Ectoderm 

Entoderm  (protentoderm) 

Archenteron 

Yolk  cells  (yolk  entoderm) 
Peristomal  mesoderm 

Yolk  plug 

Posterior  lip  of  blastopore 

Peristomal 
mesoderm 


FIG.  37. — Vertical  section  through  gastrula  of  Triton.    Hertwlg. 

yolk  cells  which  form  the  floor  of  the  cavity.  As  the  ectoderm  forms  a  com- 
plete outer  layer,  the  only  point  at  which  the  yolk  cells  now  appear  externally  is 
the  blastopore,  into  which  they  project  as  the  yolk  plug  (Fig.  37). 

It  is  possible  in  the  amphibian  gastrula  to  make  the  distinction  between  the 
entoderm  of  the  roof  which  has  grown  in  from  the  surface  and  is  continuous 
with  the  surface  ectoderm,  and  the  entoderm  of  the  floor  which  is  formed  of  yolk 
cells.  By  those  who  make  this  distinction,  the  former  is  called  the  protentoderm t 
the  latter  the  yolk  entoderm  (Fig.  37). 

In  the  case  of  the  common  frog,  the  eggs  of  which  are  so  easily  obtained 
that  they  furnish  most  satisfactory  subjects  for  study,  gastrulation  is  somewhat 
less  simple  than  in  Triton.  As  already  noted  (p.  47)  the  demarcation  between 
micromeres  and  macromeres  is  in  the  frog  very  distinct,  owing  to  the  dark  pig- 
mentation of  the  former.  This  is  shown  in  Fig.  30,  as  is  also  the  fact  that  the 
roof  of  the  segmentation  cavity  consists  of  a  surface  layer  of  strongly  pig- 


GERM  LAYERS.  55 

merited  cells,  and  beneath  this  a  layer  of  less  pigmented  cells.  Fig.  38  shows 
the  beginning  of  gastrulation,  being  a  slightly  earlier  stage  than  the  Triton 
gastrula  (Fig.  36). 

In  the  frog  (also  in  the  toad  and  salamander)  a  modification  of  the  comple- 
tion of  gastrulation  occurs,  which,  while  apparently  unimportant,  is  considered 
by  some  investigators  as  having  significance  hi  the  interpretation  of  gastrulation 
in  higher  forms,  especially  in  Mammals.  It  is  illustrated  in  Fig.  39.  The 
wedge-shaped  mass  of  yolk  cells  is  pushed  in  front  of  the  invagination  cleft  and 
carried  around  dorsally  just  beneath  the  ectoderm  (Fig.  39,  ft).  This  is  met  hi 
the  medial  dorsal  plane  by  yolk  cells  which  have  grown  up  from  the  floor  of  the 
segmentation  cavity  on  the  opposite  side  (Fig.  39,  c).  What  was  the  segmenta- 

Cells  with 
much  pigment 

,^^^^^___  ^^^^^^^  Cells  yrith 

Micromeres  -M      •*  ^B       5^         less  pigment 


Macromeres 


Invagination  (blastopore) 
FIG.  38. — From  sagittal  section  of  blastula  of  frog,  showing  beginning  of  gastrulation.     Bonnet. 

tion  cavity  thus  becomes  divided  into  a  cleft  beneath  the  ectoderm  and  a  cavity 
surrounded  by  yolk  cells.  The  cavity  is  designated  by  Bonnet  the  "  Erganzungs- 
hohle"  or  "completioti  cavity"  (Fig.  39,  c,  dte).  With  continued  enlargement 
of  the  invagination  cavity,  the  cleft-like  remains  of  the  segmentation  cavity 
beneath  the  ectoderm  becomes  obliterated  and  the  "completion  cavity"  becomes 
pressed  ventrally.  The  wall  between  the  latter  and  the  invagination  cavity 
thins  and  finally  ruptures  so  that  the  two  cavities  become  one. 

It  thus  happens  that  at  one  stage  there  are  three  cavities  (Fig.  39,  d) — (i) 
the  slit-like  remains  of  the  segmentation  cavity,  (2)  the  invagination  cavity  and 
(3)  the  so-called  "completion  cavity."  The  remains  of  the  segmentation 
cavity  is  seen  by  reference  to  the  figures  to  lie  between  the  ectoderm  externally 
and  the  protentoderm  and  yolk  entoderm  internally.  The  invagination  cavity 


56 


TEXT-BOOK  OF  EMBRYOLOGY. 


is  limited  mainly  by  protentoderm,  the  "completion  cavity"  by  yolk  entoderm. 
The  breaking  of  the  partition  between  the  invagination  cavity  and  the  "com- 
pletion cavity''  results  in  the  formation  of  the  archenteron  proper  or  primitive 
gut,  which  is  thus  lined  partly  by  protentoderm  and  partly  by  yolk  ento- 


Ectoderra 


"Wedge" 


Ectoderm 


"Wedge" 


<-  Ectoderm - 

Segment. 

cav. 
"Wedge" 


Blastopore 
Peristomal 
mesoderm 


Blastopore 


Yolk  plug 


Ectoderm 


Ectoderm 


Protentoderm 

Protentoderm 

Ant.  lip  of 
blastopore 

Yolk  plug 

Post,  lip  of 
blastopore 

FIG.  39. — Successive  stages  of  gastrulation  in  the  frog,  showing  especially  the  formation  of  the 
protentoderm,  yolk  entoderm  and  "completion  cavity."  Schultze,  Bonnet.  Com.pl.,  "Completion 
plate." 

derm,  the  two  being  from  now  on  called  simply  entoderm.  The  somewhat 
thickened  area  of  yolk  cells  at  the  junction  of  the  protentoderm  and  yolk 
entoderm  is  designated  by  Bonnet,  the  "Erganzungsplatte"  or  "completion 
plate"  (Fig.  39,  d,  e). 


GERM  LAYERS. 


57 


Gastrulation  in  Reptiles  and  Birds. 

This  is  further  modified  by  the  still  greater  increase  in  yolk,  yet  retains 
sufficient  similarity  to  the  process  in  Amphibians  and  Amphioxus  to  allow  of 
comparison. 


FIG.  40. — Surface  view  of   blastoderm  of   snake.     Hertu'ig.     Blastopore  is  represented  by  dark 
transverse  band  near  lower  side  of  figure. 

In  the  types  of  gastrulation  thus  far  described— in  Amphioxus,  Triton  and 
the  frog — the  entire  egg  is  involved  in  segmentation  and  gastrulation.  Up 
through  these  forms  there  is  a  progressive  increase  in  the  amount  of  yolk,  which 


Embryonic  disk 


Blastoderm 


Anterior  lip 

Posterior  lip 
of  blastopore 


Blastopore 
(crescentic  groove) 


FIG.  41. — Surface  view  of  embryonic  disk  of  turtle  (Emys  taurica).     Bonnet. 
X,  The  lighter  shading  represents  the  opacity  due  to  the  growth  of  the  protentoderm  (see  Fig.  42). 

in  Triton  and  still  more  in  the  frog  was  seen  to  modify  the  gastrulation  process. 
In  the  reptilian  and  the  avian  ovum  there  is  a  much  greater  increase  in  yolk 
content,  the  segmentation  being  confined  to  the  germ  disk  and  to  a  small  part  of 


58 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  underlying  yolk  (p.  56).     Just  as  cleavage  in  Reptiles   and   Birds  was 
modified  by  the  presence  of  the  large  unsegmenting  yolk  mass,  so,  for  the  same 


Ectoderm  of  embryonic  disk 


Blastopore 


Ectoderm 


Yolk  entoderm 
Blastopore 


Ectoderm 


'Completion 
plate" 


Protentoderm 


Yolk  entoderm 

Blastopore 


Peristomal  mesoderm 


Peristomal 
Blastopore       mesoderm 


"Completion 
plate" 


Remnant  of 
protentoderm 


Blastopore 


Peristomal 
mesoderm 


"Completion  plate"  Yolk  entoderm 

FIG.  42. — From  medial  vertical  sections  through  embryonic  disk  of  lizard,  showing  five  successive 
stages  in  gastrulation.     Wenckebach,  Bonnet. 

reason,  is  gastrulation  quite  modified,  as  compared  with  the  simple  process  seen 
in  Amphioxus.  At  the  same  time,  however,  it  is  possible  to  correlate  the  reptil- 
ian and  avian  gastrulation  with  gastrulation  in  the  lower  forms. 


GERM  LAYERS. 


59 


Area  apaca 
Area  pellucida 


Blastopore 
~—  (crescentic 
groove) 


It  will  be  remembered  that  in  the  discoidal  cleavage  of  Birds  the  blastula 
consists  of  a  cleft-like  segmentation  cavity,  the  roof  of  which  is  formed  by  the 
proliferating  micromeres  constituting  the  germ  disk,  while  the  floor  is  formed  by 
the  partially  segmenting  yolk  (Tig.  29).  The  former  corresponds  to  the  micro- 
meres  of  the  blastula  roof  in  Amphioxus  and  Amphibians,  the  latter  to  the 
underlying  yolk  cells.  (Compare  Figs.  26,  6,  30  and  29.) 

In  Reptiles  the  beginning  of  gastrulation  is 
evidenced  by  the  appearance  of  an  opacity  just  in 
front  of  what  may  now  be  designated  the  posterior 
margin  of  the  disk  (Fig.  40).  This  is  due  to  more 
rapid  proliferation  of  cells  at  this  point.  The 
opacity  soon  shows  a  depression  or  groove  which 
more  or  less  sharply  defines  the  posterior  margin 

of  the  disk.     It  varies  in  shape  in  different  Rep-    .  FlG-  43-— Surface  view  of  blasto- 
derm   of    unincubated    hen  s   egg. 

tiles.     It  is  frequently  crescent-shaped  and  has    Hertwig. 
been  called  the  crescentic  groove  (Fig.  41).     This 

groove  is  the  blastopore,  and  corresponds  to  the  blastoporic  invagina- 
tions  of  Amphioxus,  Triton  and  the  frog.  Soon  after  the  formation  of  the 
crescentic  groove,  there  appears  in  front  of  it  an  oval  opacity  which  extends 
forward  in  the  medial  line  (Fig.  41).  This  opacity  is  due  to  growth  of  cells 
forward  from  the  blastopore  under  the  surface  cells  as  seen  in  Fig.  42  which 
shows  the  progress  of  the  invagination  in  the  lizard.  These  figures  should  be 

compared  with  Figs.  34,  36  and  37, 
showing  the  stages  of  gastrulation  in 
Amphioxus  and  Triton,  and  especially 
with  Figs.  38  and  39  showing  gastrula- 
tion in  the  frog. 

In  Fig.  42,  i,  the  blastopore  is  seen 
as  a  distinct  invagination.  As  in  the 
frog  (Fig.  39)  the  invagination  pushes 
in  front  of  it  a  wedge-shaped  mass  of 
cells  which  extends  forward  under  the 
outer  layer.  These  cells  are  the  pro- 
tentoderm.  They  form  the  roof  and, 
with  the  underlying  yolk  entoderm,  the 
floor  of  the  new  invagination  cavity 

(Fig.  42,  2).  As  they  extend  forward  they  meet  with  a  thickened  part  of 
the  yolk  entoderm,  the  " Erganzungsplatte "  or  "completion  plate"  (Fig.  42, 
2,  3,  4  and  5;  compare  Fig.  39).  There  are  thus  present  at  this  stage,  just 
as  in  the  frog,  three  cavities,  (i)  the  slit-like  remains  of  the  segmentation 
cavity,  (2)  the  invagination  cavity  and  (3)  the  "completion  cavity."  Also 
5 


p.b.  a.b. 


y.c. 


FIG.  44. — From  vertical  longitudinal  section 
through  germ  disk  of  siskin,  showing  beginning 
of  gastrulation.  Duval. 

a.b.,  Anterior  lip  of  blastopore;  arc.,  archen- 
teron;  ec.,  ectoderm;  en.,  entoderm;  p.b.,  posterior 
lip  of  blastopore;  y.,  white  yolk;  y.c.,  yolk  cells 
(merocytes). 


60  TEXT-BOOK  OF  EMBRYOLOGY. 

as  in  the  frog  (Fig.  39),  by  a  breaking  through  of  the  two  layers — the  pro- 
tentoderm  and  the  yolk  entoderm — which  separate  the  invagination  cavity 
from  the  " completion  cavity"  in  Fig.  42,  2,  the  two  cavities  are  united  to  form 
the  archenteron  or  primitive  gut  (Fig.  42,  3,  4  and  5).  The  single-layered  germ 
disk  has  thus  become  transformed  into  a  two-layered  disk  consisting  of  an  outer 
(upper)  layer — the  ectoderm — and  an  inner  (lower)  layer — the  entoderm 
(protentoderm). 

In  Birds  the  gastrula  is  formed  in  a  manner  quite  comparable  with  its  forma- 
tion in  Reptiles.  Taking  the  hen's  egg  as  an  example,  it  will  be  remembered 
that  the  entire  segmentation  area  is  confined  to  the  germ  disk,  and  that  this  con- 
sists of  a  superficial  layer  (roof  of  segmentation  cavity)  of  small  well  defined 
cells  (micromeres)  beneath  which  is  the  cleft-like  segmentation  cavity,  while  the 
floor  of  this  cavity  is  formed  of  incompletely  segmented  yolk  (Fig.  29).  The 
beginning  of  gastrulation  is  marked  by  the  appearance  of  a  crescentic  bar  near 
the  posterior  margin  of  the  disk.  This  bar  is  due  to  more  rapid  proliferation 
of  the  cells  in  this  region,  and  in  it  there  appears  the  crescentic  groove  or  blasto- 

y.c.  a.b.    arc.         ec.    en. 


FIG.  45. — From  vertical  longitudinal  section  through  two-layered  germ  disk  of  nightingale.     Hertwig. 
a.b.,  anterior  lip  of  blastopore;  arc.,  archenteron;  ec.,  ectoderm;  en.,  entoderm  (protentoderm);  y.c., 
yolk  cells  (merocytes.) 

pore  (Fig.  43).  Just  as  described  in  lower  forms,  especially  Reptiles,  the 
micromeres  invaginate  or  fold  under  at  this  point  and  grow  forward  as  the 
protentoderm,  and  roof  in  the  new  cavity  formed  by  the  invagination  (Fig.  44). 
The  single-layered  germ  disk  is  thus  transformed  into  a  two-layered  disk  con- 
sisting of  an  outer  (upper)  layer — the  ectoderm — and  an  inner  (lowrer)  layer— 
the  entoderm  (protentoderm).  The  protentoderm  in  a  sense  replaces  the 
original  layer  of  yolk  cells  in  the  area  where  the  invagination  occurs;  the  original 
outer  layer  (micromeres)  becomes  the  ectoderm,  except  that  portion  which  is 
invaginated  to  form  the  protentoderm  (Fig.  45).  This  process  is  comparable 
with  the  disappearance  of  the  yolk  entoderm  in  Reptiles  (Fig.  42).  At  the  same 
time  the  segmentation  cavity  is  obliterated  and  the  new  cavity — invagination 
cavity — which  is  in  communication  with  the  exterior,  appears  beneath  the 
protentoderm.  (Compare  Figs.  42  and  45.) 

Under  the  central  portion  of  the  germ  disk  the  yolk  becomes  liquefied, 
while  at  the  margin  of  the  disk  it  continues  to  segment  and  give  rise  to  large 
nucleated  cells — the  yolk  entoderm.  This  is  known  as  the  area  of  supplemental 


GERM  LAYERS. 


61 


cleavage  and  apparently  corresponds  to  the  "  Erganzungsplatte "  or  "  com- 
pletion plate"  described  in  lower  forms  (p.  56;  see  also  Figs.  39  and  42). 
The  germ  disk  continues  to  spread  out  over  the  yolk  and  at  the  same  time  the 
area  of  liquifying  yolk  increases.  The  portion  of  the  disk  above  the  liquified 
yolk  appears  translucent  on  surface  view  and  is  known  as  the  area  pellucida; 
the  more  peripheral  part  of  the  disk  is  less  transparent,  being  more  closely 
attached  to  the  unchanged  yolk,  and  is  known  as  the  area  opaca. 


Area  opaca 


Hensen's  node 


Primitive  streak 


Area  pellucida 
"Completion  plate' 
Head  process 


Primitive  groove 


Post.  Hp  of 
blastopore 


FIG.  46. — Surface  view  of  embryonic  disk  of  chick.     Bonnet. 

There  next  appears  in  front  of  the  crescentic  groove  and  extending  from  its 
middle  point  forward  in  the  medial  line,  a  linear  opacity  which  is  known  as  the 
primitive  streak  (Fig.  46).  This  ends  anteriorly  in  a  knob-like  expansion — 
Hensen's  node.  According  to  Duval,  Hertwig,  Bonnet  and  others,  the  primi- 
tive streak  is  formed  in  the  following  manner.  A  notch  or  indentation  appears 
in  the  anterior  lip  of  the  transverse  blastoporic  slit  (Figs.  43  and  47,  A).  As 


Area  opaca 
t —  Area  pellucida 


— •  Primitive  streak 


Area  pellucida 
Area  opaca 
Primitive  streak 

Blastopore 
(crescentic  groove) 


FIG.  47. — Surface    views    of   blastoderms    of   Haliplana,  showing  formation  of  primitive  streak. 

Schauinsland. 

the  germ  disk  is  constantly  spreading  in  all  directions,  if  the  apex  of  this  notch 
remains  fixed,  the  extension  of  the  disk  posteriorly  must  result  in  a  drawing  out 
of  the  notch  into  a  longitudinal  slit  (Fig.  47,  B).  In  other  words,  the  horns  of 
the  crescentic  slit  are  pushed  together  to  form  a  longitudinal  slit.  And  as  the 
two  lips  of  the  slit  come  together  they  fuse,  and  the  line  of  fusion  is  marked  by  a 
shallow  groove,  the  primitive  groove.  At  the  anterior  end  of  the  slit  in  the  region 


62 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  Hensen's  node,  there  is  a  small  area  where  fusion  does  not  occur,  thus  leaving 
a  small  opening  which  communicates  with  the  cavity  of  the  primitive  gut.  Since 
the  primitive  groove  is  formed  from  the  original  crescentic  slit,  and  the  original 
crescentic  slit  is  the  blastopore,  the  primitive  groove  may  be  considered  as  a 
modified  blastopore  in  which  the  only  opening  is  at  Hensen's  node.  The 
primitive  groove  lies  in  the  medial  line  of  the  primitive  streak;  and  since  the 
primitive  groove  is  a  modified  blastopore,  the  two  primary  germ  layers  are  fused 


ec.  en.  arc. 


Lb.    y.p. 


FIG.  48. — From  transverse  section  through  Hensen's  node — germ  disk  of  chick  of  2  to  6  hours'  incu- 
bation.    Duval.    For  lettering  see  FIG.  49. 

at  the  lips  of  the  primitive  groove  (Figs.  48  and  49).  To  this  fusion  is  due  the 
opacity  which  constitutes  the  primitive  streak  as  seen  from  the  surface  (Fig.  46). 
After  the  formation  of  the  primitive  groove  and  streak  there  is  no  longer  any 
specially  marked  definition  of  the  posterior  margin  of  the  germ  disk,  the  entire 
circumference  having  a  uniform  demarcation. 

Very  soon  after  the  formation  of  the  primitive  streak  a  new  opacity  appears 
which  extends  forward  in  the  medial  line  from  Hensen's  node  (anterior  lip  of 
the  blastopore).  This  is  known  as  the  head  process,  or  "primitive  intestinal 


en.  ec.  p.g. 


FIG.  49. — From  transverse  section  through  primitive  groove — germ  disk  of  chick  of  2  to  6  hours'  incu- 
bation.    Duval. 

arc.,  Archenteron;  ec.,  ectoderm;  en.,  entoderm;  7.6.,  lip  of  blastopore;  p.g.}  primitive  groove;  y.t 
yolk;  y.p.,  yolk  plug. 

cord"  (Bonnet)  (Fig.  50).  This  new  opacity  is  due  to  growth  of  cells  under  the 
ectoderm,  the  cells  constituting  the  protentoderm.  As  a  matter  of  fact,  this 
formation  of  the  protentoderm  is  a  further  extension  of  that  same  process 
which  began  with  the  crescentic  groove  (blastopore)  invagination  and  continued 
during  the  transformation  of  the  crescentic  groove  into  the  primitive  streak 
(still  the  blastopore).  Consequently  this  whole  process  from  the  formation  of 
the  crescentic  groove  up  entirely  through  the  formation  of  the  protentoderm,  is 


GERM  LAYERS.  63 

homologous  with  the  simpler  protentoderm  formation  from  the  crescentic 
groove  (blastopore)  in  Reptiles.  (Compare  Fig.  51  with  Fig.  42.)  As  the 
protentoderm  grows  forward  in  the  medial  line  it  apparently  replaces  the  yolk 
entoderm,  so  that  the  roof  of  the  new  cavity — the  archenteron — is  formed  of 
protentoderm.  The  area  where  the  protentoderm  fuses  with  the  yolk  entoderm 
is,  as  in  Reptiles,  the  "completion  plate." 

The  only  real  difference  between  gastrulation  in  Reptiles  and  in  Birds  is 
that  in  Birds  the  crescentic  groove  (original  blastopore)  becomes  transformed 
into  the  primitive  groove  which  remains  open  only  at  its  anterior  end  (Hensen's 
node) , while  in  Reptiles  the  blastopore  may  be  of  any  form,  crescentic,  round,  oval, 
etc.,  but  does  not  usually  present  a  longitudinal  linear  appearance.  Thus  in  the 
latter  case  the  primitive  intestinal  invagination  (the  head  process,  "primitive 


_       "Area  opaca 
Area  pellucida 

•"Completion  plate* 


Hensen's  node 
Primitive  streak 


Head  process 


FIG.  50. — Surface  view  of  chick  blastoderm.     Bonnet. 

intestinal  cord")  grows  forward  from  the  original  point  of  invagination  near  the 
posterior  margin  of  the  disk. 

Gastrulation  in  Mammals. 

Reference  to  the  description  of  segmentation  in  the  mammalian  ovum  and 
its  peculiarities  (p.  48)  makes  it  evident  that  these  peculiarities  must  deter- 
mine further  modifications  in  the  development  of  the  germ  disk  as  compared 
with  lower  forms.  It  will  be  remembered  that  segmentation  in  the  mamma- 
lian ovum  had  been  carried  to  the  differentiation  of  two  kinds  of  cells  (p.  48), 
an  outer  cell  layer  (trophoderm)  and  an  inner  cell  mass  (Fig.  33).  In  lower 
forms  the  first  cell  differentiation  came  with  the  formation  of  the  two  primary 
germ  layers,  the  ectoderm  and  the  entoderm,  and  these  with  the  enclosed  cavity 
constituted  the  gastrula.  The  first  cell  differentiation  in  Mammals  has,  how- 
ever, an  entirely  different  significance,  the  trophoderm  having  nothing  to 
do  with  the  formation  of  the  embryo  but  being  destined  to  give  rise  to  extra- 
embryonic  structures.  It  is  the  cells  of  the  inner  cell  mass  or  embryonal  bud 


64 


TEXT-BOOK  OF  EMBRYOLOGY. 


which  give  rise  to  the  embryonic  structures  proper.  In 
other  words,  the  inner  cell  mass  alone  is  the  anlage  of 
the  embryo  and  this  at  this  stage  shows  no  differentiation 
into  germ  layers  (Fig.  33). 

The  initial  step  in  the  formation  of  the  two  primary 
germ  layers  in  the  mammalian  ovum  is  the  differentia- 
tion and  splitting  off  of  the  deeper  cells  of  the  inner 
cell  mass  (Fig.  52,  a).  These  cells  are  the  primitive 
entoderm  and,  as  a  single  layer,  soon  extend  around 
the  vesicle  until  they  completely  line  it.  They  lie  in 
apposition  to  the  cells  of  the  trophoderm  except  where 
separated  from  them  by  the  remaining  cells  of  the  inner 
cell  mass.  While  the  primitive  entoderm  is  extending 
around  the  vesicle,  vacuolization  of  the  more  superficial 
cells  of  the  inner  cell  mass  takes  place  (Fig.  52,  b)  and 
results  in  the  formation  of  a  cavity  between  the  over- 
lying  trophoderm  and  the  still  remaining  cells  of  the 
inner  cell  mass.  This  cavity  is  known  as  the  amniotic 
cavity  (Fig.  52,  c).  Its  roof  is  formed  by  the  tropho- 
derm,  wThile  its  floor  is  formed  by  the  remaining  cells 
of  the  inner  cell  mass,  which  have  now  become  arranged 
in  a  distinct  layer  and  constitute  the  embryonic  disk 
(Fig.  52,  c).  The  latter  lies  directly  upon  the  primary 
entoderm  and  constitutes  the  surface  layer  of  the 
embryo — the  ectoderm.  Thus  at  this  stage  of  develop- 
ment,  the  roof  of  the  amniotic  cavity  is  composed  of 
cells  which  are  to  give  rise  to  extraembryonic  structures, 
or  envelopes,  while  the  floor  is  composed  of  the  two- 
layered  embryo  now  consisting  of  ectoderm  and  ento- 
derm.  Those  investigators  who  attempt  to  homologize 
the  early  differentiation  of  cells  in  Mammals  and  in 
lower  forms,  consider  this  first  formed  entoderm  in 
Mammals  as  identical  with  the  yolk  entoderm  of  lower 
forms  and  so  designate  it,  although  it  does  not  consist 
of  yolk  cells.  The  protentoderm  is  formed  later  (p.  66). 

Considering  as  a  specific  example  gastrulation  in 
the  dog,  it  is  to  be  noted  that  just  before  gastrulation 
begins,  the  embryonic  disk  of  the  dog  is  essentially 
similar  to  that  of  the  bat  which  has  been  described 
(see  above),  with  the  exception  that  in  the  dog  the 
embryonic  disk  is  not  roofed  in  by  the  amnion.  At 


GERM  LAYERS. 


65 


the  stage  corresponding  to  Fig.  52,  c,  the  embryonic  disk  of  the  dog  presents  on 
surface  view  a  uniform  appearance. 

The  first  differentiation  noticeable  in  the  disk  is  an  opacity  at  what  now 
becomes  defined  as  the  posterior  margin  of  the  disk  (Fig.  53).     As  the  em- 


FIG.  52. — Sections  of  blastodermic  vesicle  of  bat,  showing  (a)  formation  of  the  entoderm  an  3 
(b  and  c)  of  the  amniotic  cavity,     van  Beneden. 

bryonic  disk  increases  in  size  a  linear  opacity  appears  extending  from  the 
opacity  at  the  posterior  margin  of  the  disk  forward  in  the  medial  line  to  a  point 
somewhat  anterior  to  the  center  of  the  disk.  The  appearance  (Fig.  53)  is 
strikingly  similar  to  that  of  the  chick  at  the  same  stage  (Fig.  46).  The  posterior 
opacity  corresponds  to  the  crescentic  groove,  the  linear  opacity  to  the  primitive 


66 


TEXT-BOOK  OF  EMBRYOLOGY. 


streak,  its  anterior  club-shaped  end  to  Hensen's  node.  If  we  assume  the  same 
transformation  of  the  crescentic  groove  into  the  primitive  groove,  the  two  to- 
gether corresponding  to  the  blastopore,  the  condition  is  quite  analogous  to  that 
in  the  chick  (p.  61). 

At  a  slightly  later  stage  than  shown  in  Fig.  53,  a  new  opacity  appears  ex- 
tending forward  in  the  medial  line  from  Hensen's  node  (Fig.  54,  a).  This  is 
the  head  process,  and  may  be  considered  as  homologous  with  the  head  process  in 
the  chick.  (Compare  Fig.  54,  a,  with  Fig.  50.)  The  opacity  is  due  to  a  plate 
or  cord  of  cells  which  grows  from  the  region  of  Hensen's  node  forward  under  the 
surface  layer  of  cells  (ectoderm)  (Fig.  55).  On  the  assumption  that  Hensen's 


Si 


Embryonic  disk 


Hensen's  node  •    £*,'*;»« 


FIG.  53. — Embryonic  disk  of  dog.     Bonnet.     The  letters  and  figures  on  the  right  (Si-S4)  indicate 

planes  of  sections  shown  in  Fig.  75. 

node  is  the  anterior  lip  of  the  blastopore,  this  plate  of  cells  may  possibly  be  con- 
sidered as  homologous  with  the  invaginated  cells  which  form  the  protentoderm 
in  Reptiles  and  Birds.  (Compare  Figs.  42,  51  and  55.)  Consequently,  since 
the  protentoderm  in  the  lower  forms  was  designated  the  "primitive  intestinal 
cord"  (Urdarmstrang),  so  in  Mammals  this  invaginated  cord  of  cells  maybe 
called  the  "primitive  intestinal  cord"  (protentoderm)  (Fig.  54). 

In  Reptiles  it  has  been  seen  that  as  the  protentoderm  grows  forward  under 
the  surface  layer  (ectoderm)  the  yolk  entoderm  for  some  distance  disappears, 
and  the  protentoderm  fuses  with  the  remaining  yolk  entoderm  in  an  area 
known  as  the  completion  plate  (Fig.  42).  In  the  chick  also  it  has  been  stated 
that  a  similar  process  occurs  (p.  62).  In  Mammals  the  yolk  entoderm,  which 


GERM  LAYERS. 


67 


Embryonic  disk 
Hensen's  node 


Primitive  streak 

and  groove 

Embryonic  disk 


Completion  plate 

I  Head  process 

Prim.  int.  cord 
(protentoderm) 


w 


Ectoderm 


Yolk  entoderm 


Ectoderm 


Si 


Yolk  entoderm 

Ectoderm 

Mesoderm 


Completion  plate 

Medullary  folds 


Yolk  entoderm 


Yolk  entoderm 


Chordal  plate  (protentoderm) 
Primitive  groove 


Mesoderm 


Mesoderm 


Mesoderm 


Mesoderm 


Mesoderm 


Yolk  entoderm 


FIG.  54. — Surface  view  of  embryonic  disk  of  dog  and  transverse  sections  of  same      "Bonnet, 
a,  Disk  somewhat  further  advanced  than  that  in  Fig.  53;  the  letters  and  figures  (Si-S5)  indicate  planes 
of  sections  in  b.     m.  gr.,  medullary  groove. 


68 


TEXT-BOOK  OF  EMBRYOLOGY. 


was  present  from  the  time  of  its  differentiation  from  the  inner  cell-mass  (Fig.  52), 
apparently  disappears  or  is  replaced  by  the  protentoderm,  as  the  latter  grows 
forward  under  the  ectoderm  and  finally  the  protentoderm  becomes  continuous 
at  its  anterior  border  with  the  yolk  entoderm  that  remains.  The  area  where  the 
two  become  continuous  is  the  "completion  plate"  (Fig.  55). 

The  disappearance  of  the  yolk  entoderm,  or  its  replacement  by  protentoderm, 
occurs,  however,  only  in  a  linear  area;  that  is,  the  protentoderm  grows  forward 
only  as  a  narrow  band  of  cells  which  replaces  a  correspondingly  narrow  band  of 


Mesoderm    Blastopore 


Embryonic  disk 


Ectoderm 


Mesoderm 


Yolk  entoderm  Chordal  plate  Completion  plate 

Fro.  55. — Medial  section  of  germ  disk  of  bat.     van  Beneden. 

yolk  entoderm.  And  since  this  strip  of  protentoderm  is  destined  to  give  rise  to 
the  notochord,  it  is  sometimes  known  as  the  "chordal  plate"  (Fig.  54,  S3). 
From  the  manner  of  formation  of  the  "  chordal  plate,"  it  is  continuous  along 
each  side  with  the  yolk  entoderm  (Fig.  54,  S2). 

No  human  ovum  showing  gastrulation  has  been  observed.  What  is  known 
of  the  formation  of  the  germ  layers  in  man  is  discussed  on  p.  85. 

FORMATION  OF  THE  MIDDLE  GERM  LAYER— MESODERM. 

Mesoderm  Formation  in  Amphioxus. — In  such  a  simple  type  as  Amphi- 
oxus  the  formation  of  the  middle  germ  layer  is  readily  observed  and  there  is 
consequently  no  question  as  to  the  manner  in  which  it  arises.  In  higher  forms, 
however,  the  origin  of  the  mesoderm  has  been  and  still  continues  to  be  one  of 
the  most  difficult  of  embryological  problems. 

In  the  two-layered  Amphioxus  gastrula  the  mesoderm  first  appears  as  two 
symmetrical  evaginations  of  the  entoderm  which  push  out  dorso-laterally  from 
the  archenteron  (Fig.  56,  a).  That  part  of  the  entoderm  which  lies  between  the 
two  mesodermic  evaginations  is  composed  of  somewhat  higher  cells  than  those 
of  the  developing  mesoderm  and  constitutes  the  anlage  of  the  notochord  (chorda). 
The  lips  of  the  mesodermic  evaginations  next  come  together  (Fig.  56,  b)  in  such  a 
manner  that  the  mesoderm  becomes  completely  separated  from  the  archenteron 
(Fig.  56,  c).  While  this  separation  is  taking  place,  the  mesodermic  evaginations 
divide  transversely  into  a  number  of  segments  which  lie  on  each  side  of  the 
medial  line  and  are  known  as  the  mesodermic  somites — primitive  segments 
(Fig.  57).  Meanwhile,  the  chorda  anlage  is  being  transformed  into  the  chorda 


GERM  LAYERS. 


69 


itself.  This  transformation  is  initiated  by  an  evagination  dorsalward  of  the 
entodermic  cells  which  lie  between  the  two  mesodermic  evaginations  (Fig.  56,  c), 
these  cells  soon  becoming  constricted  off  as  the  solid  cord  of  cells  which  consti- 
tute the  notochord  (Fig.  56,  d).  With  the  separation  of  the  chorda,  the  remain- 
ing entoderm  unites  across  the  medial  line  and  becomes  the  epithelium  (en- 
toderm)  of  the  primitive  intestine.  The  formation  of  the  mesodermic  somites 
begins  near  the  middle  of  the  embryo  and  proceeds  caudally.  There  is  thus  at 
this  stage  a  row  of  somites  on  each  side  of  the  medial  line,  the  number  of  somites 


Notochord 


Mesodenn 
Notochord 


Entoderm 


Parietal 
mesoderm 
Visceral 
mesoderm 

Intestine 
Entoderm 


FIG.  56. — From  transverse  sections  through  Amphioxus  embryos,  showing  successive  stages  in  for- 
mation of  mesoderm,  neural  tube  and  notochord.     Bonnet. 

increasing  by  constant  differentiation  and  pushing  forward  of  more  segments 
(somites)  from  the  caudal  unsegmented  mesoderm  (Fig.  57). 

While  the  above  described  changes  have  been  taking  place,  those  ectodermic 
cells  which  lie  along  the  dorsal  medial  line  become  higher  and  form  the  bottom 
of  a  shallow  longitudinal  groove.  This  is  known  as  the  neural  groove,  while  the 
folds  which  bound  the  groove  on  each  side  are  known  as  the  neural  folds  (Fig. 
56,  a).  From  the  crests  of  the  folds  the  remaining  lower  ectodermic  cells  grow 
across  and  meet  in  the  medial  line  thus  forming  the  surface  ectoderm  (Fig.  56, 
b  and  c).  The  neural  groove  next  deepens,  the  neural  folds  bending  dorsally 


70 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  toward  the  medial  line  where  they  finally  meet,  thus  converting  the  groove 
into  a  closed  canal  or  tube,  the  neural  tube  (Fig.  56,  d;  see  Chap.  XVII).  As  the 
ectoderm  grows  over  the  neural  groove  and  as  the  latter  becomes  transformed 
into  the  neural  tube,  there  remains  anteriorly  an  opening  from  the  exterior  into 


Anterior  (cephalic)  end 


Epidermis 
(ectoderm) 


Entoderm 


Coelom 
(myocoel) 


Archenteron 


Unsegmented 
mesoderm 


Posterior  (caudal)  end 

FIG.  57. — From  horizontal  section  through  Amphioxus  embryo  with  5  primitive  segments;  seen  from 

dorsal  side.     Hatschek. 

The  communication  between  the  cavities  of  the  primitive  segments  (coelom)  and  the  archenteron 
can  be  seen  in  the  last  4  segments. 

the  neural  tube.  This  is  known  as  the  neuropore  (Fig.  58) .  Caudally,  the  neural 
groove  extends  over  the  region  of  the  blastopore  and  as  the  groove  closes  over  to 
form  the  neural  tube,  it  embraces  the  blastopore  which  now  becomes  closed 


Neuropore 


Primitive  segment  — 
Coelom  (myocoel) 

Intestine 


Epidermis  (ectoderm) 
Neural  tube 


Anterior   )  lip  of 
Posterior  j  blastopore 

Unsegmented 
mesoderm 


FIG.  58. — From  vertical  section  through  Amphioxus  embryo  with  5  primitive  segments.     Hatschek. 


externally  but  opens  into  the  neural  tube.  This  opening,  which  thus  connects 
the  neural  tube  with  the  intestine,  is  known  as  the  neurenteric  canal  (Fig.  58), 
and  it  is  a  rather  remarkable  fact  that  while  giving  rise  to  no  adult  organ,  it  is 
found  without  exception  in  all  Vertebrates  which  have  been  studied. 


GERM  LAYERS.  71 

The  mesodermic  somites  meanwhile  extend  their  edges  ventrally  between 
the  ectoderm  and  the  entoderm  until  they  meet  and  fuse  in  the  midventral  line 
(Figs.  56,  d  and  59).  A  transverse  constriction  next  appears  which  cuts  off  the 
ventral  extension.  The  latter  is  known  as  the  lateral  plate,  wrhile  the  remaining 
dorsal  part  is  still  designated  the  primitive  segment.  (Compare  Fig.  56,  d}  with 

Fig.  59)- 

The  primitive  segments  retain  their  segmental  character.  The  lateral 
plates,  on  the  other  hand,  do  not  retain  their  segmented  condition  but  fuse,  their 
cavities  uniting  to  form  the  primitive  body  cavity  or  ccelom,  which  is  the  anlage 
of  the  large  serous  cavities  of  the  adult.  The  outer  part  of  the  lateral  plate  or 

Neural  tube 

^»  Notochord 

Epidermis  (ectoderm) 

^^JS/^>^t^Q"\  m^^^ 

'  Primitive  segment 

Muscle  plate 
Cutis  plate 
Myocoel 


Splanchnocoel 

Parietal  mesoderm  ~) 

Mat.  plate 
Entoderm -W^^^H^S/^ Visceral  mesoderm  J 


Ventral       Subintestinal 
mesentery  vein 

FIG.  59. — Diagram  to  show  differentiation  of  primitive  segment  into  muscle  plate  (myotome)  and 
cutis  plate  and  relation  of  myocoel  and  splanchnocoel.     Bonnet.     Compare  with  Fig.  56,  d. 

parietal  mesoderm,  with  the  adjacent  ectoderm,  forms  the  somatopleure  (Fig.  59). 
The  inner  layer  of  the  lateral  plate,  the  visceral  mesoderm,  with  the  adjacent 
entoderm,  forms  the  splanchnopleure  (Fig.  59). 

At  the  caudal  end  of  the  embryo,  just  in  front  of  the  neurenteric  canal,  there 
exists  at  this  stage  an  area  where  the  germ  layers  have  not  become  differentiated 
to  form  special  structures.  In  this  area,  cell  proliferation  is  especially  active  and 
from  it  cells  are  derived  for  the  completion  of  the  neutral  tube,  chorda,  somites, 
intestine,  etc.  By  this  means  the  growth  of  the  embryo  in  length  is  provided 
for  (Figs.  57  and  58). 

The  Amphioxus  embryo  at  this  stage  thus  consists  of: 

1.  Ectoderm. — Surface  ectoderm  and  neural  tube. 

2.  Mesoderm. — Somites;  parietal  mesoderm  and  visceral  mesoderm 

enclosing  the  ccelom. 

3.  Entoderm. — Chorda  and  wall  of  primitive  intestine. 


72 


TEXT-BOOK  OF  EMBRYOLOGY. 


Mesoderm  Formation  in  Amphibians. — In  Amphibians  the  formation  of 
the  mesoderm  is,  like  gastrulation,  modified  by  the  presence  of  many  large  yolk 
cells.  Taking  for  an  example  the  water  salamander  (Triton),  which  furnishes 


Blastopore 


Ectoderm 
Parietal  mesoderm 

Visceral  mesoderm 


Entoderm 


Primitive  gut 
FIG.  60. — From  transverse  section  through  Triton  embryo  at  region  of  blastopore.     Hertwig. 

perhaps  the  simplest  type  of  mesoderm  formation  in  Amphibians,  only  in  the 
region  of  the  blastopore  does  the  mesoderm  formation  conform  at  all  closely  to 
that  of  Amphioxus.  In  this  region  the  middle  germ  layer  is  seen  to  consist  of 
two  lateral  evaginations  which  push  out  between  the  entoderm  and  ectoderm, 

Notochord  anlage       Neural  plate 

Parietal  mesoderm 
Visceral  mesoderm 

Primitive  gut 
Entoderm 


FIG.  61. — From  transverse  section  through  Triton  embryo  in  front  of  blastopore.     Hertwig. 

each  containing  a  cavity,  the  primitive  body  cavity  (Fig.  60).  More  cranially 
the  mesoderm  grows  out  laterally  between  the  entoderm  and  ectoderm,  not  as 
two  hollow  evaginations,  but  as  solid  plates  of  cells  which  only  later  separate  into 
two  layers  and  enclose  the  primitive  body  cavity  (Fig.  61).  Hertwig  considers 


GERM  LAYERS. 


73 


mesoderm  formation  in  Triton  entirely  analogous  to  its  formation  in  Amphioxus, 
the  solid  plate  of  cells  being  really  two  layers  enclosing  the  body  cavity,  but 
pressed  together  by  the  large  amount  of  yolk.  Although  the  mesoderm  de- 
veloped in  the  region  of  the  blastopore  and  that  which  originates  more  cranially 
are  continuous  in  front  of  the  blastopore,  it  is  convenient  to  designate  the 
former  the  peristomal,  the  latter  the  gastral  mesoderm. 

The  separation  of  the  mesoderm  into  a  dorsal  segmented  part  and  a  ventral 
unsegmented  part  containing  the  body  cavity;  the  formation  of  the  notochord 
between  the  two  lateral  plates  of  mesoderm  by  a  constricting  off  of  cells  from  the 
entoderm;  the  closure  of  the  primitive  intestine  beneath  the  notochord;  the 
development  of  the  neural  groove  and  folds  with  their  final  closure  to  form  the 
neural  tube;  and  the  extension  of  ectoderm  over  their  surface  to  form  the  surface 
ectoderm  (epidermis),  are  processes  quite  similar  to  the  formation  of  the  same 


Myocoel 


Xeural 
tube 


Coelom 


Primitive  segment 


mesoderm 


Yolk  cells 
(entoderm) 

FIG.  62. — From  transverse  section  through  dorsal  part  of  Triton  embryo.     Hertwig. 

structures  in  Amphioxus  (Fig.  62).  Also  as  in  Amphioxus,  the  differentia- 
tion of  these  structures  is  more  advanced  cranially  and  gradually  extends 
caudally  where  for  some  time  there  exists  a  growth  area  in  which  they  are  not  as 
yet  differentiated. 

In  the  frog  the  formation  of  the  mesoderm  is  sufficiently  different  from 
Amphioxus  and  Triton  to  make  its  correlation  somewhat  difficult.  In  the  frog 
apparently  all  trace  of  mesodermic  evagination  is  lost.  Taking  a  transverse 
section  through  the  frog's  gastrula  at  a  stage  when  the  blastopore  is  still  circular 
and  widely  open  (Fig.  39),  the  mesoderm  is  seen  as  a  flat  plate  of  cells  which 
blends  in  the  medial  line  with  the  protentoderm  and  ventrally  with  the  yoke 
entoderm  (p.  74,  Fig.  63).  The  mesoderm  has  here  arisen  apparently  by  a 
splitting  off  of  a  layer  of  cells  from  the  protentoderm,  the  remaining  cells  of  the 
protentoderm  forming  the  roof  of  the  primitive  gut.  Beginning  at  the  sides,  the 


74  TEXT-BOOK  OF  EMBRYOLOGY. 

separation  of  the  mesoderm  extends  dorsally  to  the  chorda  and  ventrally,  as 
indicated  by  arrows  in  Fig.  63,  splitting  off  the  superficial  cells  of  the  yolk 
entoderm  until  the  mesoderm  becomes  completely  separated  from  the  yolk  cells. 
On  each  side  of  the  notochord  the  mesoderm  shows  a  shallow  longitudinal  groove 
(Fig.  64)  which  has  been  interpreted  by  some  as  the  homologue  of  the  meso- 
dermic  evagination  of  Amphioxus.  This  groove  does  not  persist,  however,  and 
has  nothing  to  do  with  the  formation  of  the  body  cavity.  The  latter  in  the  frog 
results  not  from  evagination  but  from  a  splitting  of  the  originally  solid  mesoder- 
mic  plates.  It  is  to  be  noted,  however,  that  while  the  ccelom  does  not  originate 
as  an  evagination  from,  and  is  never  connected  with,  the  primitive  intestine, 
the  mesoderm  itself  consists  of  cells  which  have  split  off  from  the  wall  of  the 


Chorda  anlage 


f  Ectoderm 


Yolk  entoderm 


Remnant  of 
segmentation  cavity 


FIG.  63.— Transverse  section  of  embryo  of  frog  (Rana  fusca).     Bonnet.    The  section  is  taken  in  front 

of  (anterior  to)  the  blastopore. 

primitive  intestine  (entoderm),  and  that  it  is  within  this  group  of  cells  that  the 
ccelom  finally  appears.  Of  the  yolk  cells,  only  the  outermost  (most  peripheral) 
have  to  do  with  the  formation  of  intestinal  epithelium,  the  remainder  being 
ultimately  used  up  for  the  nutrition  of  the  embryo  (Fig.  65). 

The  formation  of  the  neural  groove  and  neural  tube  from  the  ectoderm  and 
the  separation  of  the  chorda  anlage  from  the  rest  of  the  entoderm  are  much  the 
same  as  in  Triton. 

Mesoderm  Formation  in  Reptiles  and  Birds.— The  actual  origin  of 
the  mesoderm  in  these  forms  is  very  difficult  to  determine  owing  to  the  pecu- 
liarities of  gastrulation  which  in  turn  are  due  to  the  greatly  increased  amount 
of  yolk.  In  the  lower  forms  it  has  been  seen  that  the  mesoderm  is  primarily  a 
derivative  of  the  entoderm  (Amphioxus,  Fig.  56),  or  of  protentoderm  and  yolk 


GERM  LAYERS. 


75 


entoderm  (frog,  Fig.  53).  One  would  expect,  a  priori,  that  the  mesoderm  has 
a  similar  origin  in  the  higher  forms,  even  if  the  entoderm  has  assumed  a  differ- 
ent form  on  account  of  the  fact  that  the  yolk  plays  little  or  no  part  in  the  process 


Ectoderm 


Mesoderm 


Chorda  anlage 


Entoderm 


FIG.  64. — Transverse   section  through  dorsal  part  of  embryo  of  frog  (Rana  fusca).     Ziegler. 
x,  Groove  indicating  evagination  to  form  mesoderm. 

of  imagination.  As  a  matter  of  fact,  observations  do  to  a  certain  extent  fulfill 
the  expectation,  but,  on  the  other  hand,  it  is  not  possible  to  trace  the  earliest 
steps  in  its  formation  with  anything  like  the  degree  of  certainty  with  which  it 
can  be  traced  in  the  lower  forms. 


Neural  crest 

Neural  canal 

Primitive  segment 

Notochord 

Coelom 


Ventral  mesoderm  < 


Yolk  cells 


?•  Ectoderm 


Parietal  mesoderm 
Visceral  mesoderm 


Entoderm 


FIG.  65. — Transverse  section  through  embryo  of  frog  (Rana  fusca).     Bonnet. 


Taking  the  chick  again  as  an  example,  the  mesoderm  appears  first  in  the 
region  of  the  primitive  groove  (blastopore).  Transverse  sections  through  this 
region  show  the  mesoderm  as  several  layers  of  small  irregular  cells  interposed 
laterally  between  the  ectoderm  and  entoderm.  In  the  medial  line,  or  line  of  the 


76 


TEXT-BOOK  OF  EMBRYOLOGY. 


primitive  groove,  all  three  germ  layers  are  blended  into  a  solid  mass  of  cells 
(Fig.  66) .  On  the  ground  that  the  primitive  groove  is  the  blastopore,  the  meso- 
derm  here  is  the  peristomal  mesoderm,  the  homologue  of  the  peristomal 
mesoderm  which  encircles  the  blastopore  in  lower  forms  (Fig.  37). 


Primitive  groove  and  folds 


Ectoderm 


—  Ectoderm 

—  Mesoderm 

—  Entoderm 


FIG.  66. — Transverse  sections  of  blastoderm  of  chick  (21  hours'  incubation).     Hertwig. 

a,  Section  through  primitive  groove,  posterior  to  Hensen's  node. 

b,  Section  through  Hensen's  node. 

At  a  somewhat  later  stage,  after  the  head  process  appears,  sections  through 
the  head  process  also  show  all  three  germ  layers.  Here  the  ectoderm  is  a  sepa- 
rate layer;  but  the  entoderm  and  mesoderm  are  fused  in  the  medial  line;  that 

Head  process        Neural  plate 


Ectoderm 
Mesoderm 
—  Entoderm 


Yolk  cell  - 


—  Archenteron 


Yolk 


FIG.  67. — Transverse  section  of  blastoderm   of  chick   (21   hours'  incubation).  Hertwig.     Section 
through  head  process,  anterior  to  Hensen's  node. 

is,  in  the  line  of  the  "primitive  intestinal  cord."  Laterally,  the  layers  are  all 
separate,  a  cleft  existing  between  the  mesoderm  and  the  ectoderm  and  another 
between  the  mesoderm  and  the  entoderm  (Fig.  67).  Since  the  mesoderm  in 
the  region  of  the  head  process  is  in  front  of  the  primitive  groove  (blastopore) 


GERM  LAYERS.  77 

and  appears  in  connection  with  the  "  primitive  intestinal  cord/'  it  is  the  gastral 
mesoderm,  the  homologue  of  the  gastral  mesoderm  described  in  lower  forms 
(Fig.  63).  Here  also,  as  in  the  case  of  the  peristomal  mesoderm,  the  mesoderm 
is  primarily  a  solid  plate  of  cells.  Furthermore,  immediately  in  front  of  the 
primitive  groove  the  gastral  mesoderm  is  continuous  with  the  peristomal. 

At  a  still  later  stage  the  gastral  mesoderm  is  found  to  be  separated  from  the 
entoderm,  so  that  the  "primitive  intestinal  cord"  (now  the  notochord)  separates 
the  mesoderm  of  the  two  sides  in  the  medial  line  (Fig.  68). 

Neural  plate  Xotochord 

'        Ectoderm 
— '  Mesoderm 

•:-" '  Entoderm 
•— "" "  Archenteron 


FIG.  68. — Transverse  section  of  blastoderm  of  chick  (40  hours'  incubation).     Hertwig. 
Section  taken  short  distance  anterior  to  Hensen's  node. 

Comparing  the  conditions  in  sections  through  the  head  process  in  the  chick 
with  sections  through  the  body  region  of  the  frog  (Figs.  63  and  64),  a  fairly 
clear  homology  may  be  drawn. 

While  in  the  stages  just  described  in  the  chick  the  mesoderm  is  present  and 
interposed  between  the  ectoderm  and  entoderm,  the  crucial  point  is  its  actual 
origin.  In  the  lower  forms  it  originated  from  the  entoderm,  that  is,  from  the 
cells  which  have  been  invaginated  at  the  blastopore.  In  the  chick  the  blasto- 
pore;  which  is  crescent-shaped,  is  transformed  into  a  longitudinal  structure — 


Mesoderm       Primitive  groove 


_  FIG.  69. — Transverse  section  of  blastoderm  of  chick  (10  hours'  incubation).     Hertwig. 
Section  taken  through  primitive  groove  and  streak. 

the  primitive  groove — but  still  the  blastopore.  As  the  crescentic  blastopore 
becomes  longitudinal,  the  two  horns  come  together  and  fuse  (see  p.  61),  and 
the  line  of  fusion  still  represents  the  area  of  imagination,  where  some  of  the 
surface  cells  have  grown  under  the  remaining  surface  cells  to  form  the  entoderm 
(protentoderm) .  And  it  is  along  this  area  of  invagination  that  the  mesoderm 
first  appears.  In  very  early  stages  there  is  an  especially  active  cell  proliferation 
in  the  thickened  layer  of  cells  which  represents  the  primitive  streak.  This 
activity  gives  rise  to  a  mass  of  cells  which  lie  immediately  beneath  the  primitive 


78 


TEXT-BOOK  OF  EMBRYOLOGY. 


groove  and  represent  the  first  mesodermal  cells  (Fig.  69).  It  is  reasonable  to 
assign  the  origin  of  these  cells  to  the  cells  which  have  been  invaginated  along  the 
line  of  the  primitive  groove  (blastopore).  These  invaginated  cells  constitute 
the  protentoderm,  hence  the  mesodermal  cells  may  be  considered  as  derivatives 
of  the  protentoderm. 

As  proliferation  continues,  the  mesodermal  cells  spread  out  between  the 
ectoderm  and  entoderm  (which  is  here  yolk  entoderm)  (Fig.  70).     Finally,  the 


Ectoderm    p.gr. 


Mesoderm 


—  Ectoderm 

—  Entoderm 

Yolk 


FIG.  70. — Transverse  section  of  blastoderm  of  chick  (slightly  older  than  that  shown  in  Fig.  69). 

Hertwig. 
Section  taken  through  primitive  groove  (p.gr.)  and  streak. 

mesoderm  fuses  with  the  yolk  entoderm,  so  that  all  three  germ  layers  are  fused 
beneath  the  primitive  groove  (Fig.  66).  The  fusion  between  the  mesoderm  and 
yolk  entoderm  in  this  region  is  a  secondary  matter. 

That  the  peristomal  mesoderm  is  a  derivative  of  the  invaginated  cells  is 
even  more  clearly  demonstrated  in  Fig.  71,  in  which  the  two  lips  of  the  blasto- 
pore have  not  yet  fused. 

Primitive  fold         Primitive  groove 


FIG.  71. — Transverse  section  through  primitive  streak  and  primitive  groove  of  Diomedea. 

Schauinsland. 

In  front  of  the  primitive  groove,  that  is,  in  the  region  of  the  head  process,  the 
gastral  mesoderm  is  at  first  seen  to  be  continuous  with  the  "primitive  intestinal 
cord"  (Fig.  67);  later  it  becomes  separated  on  each  side  from  the  "primitive 
intestinal  cord"  (now  the  notochord).  While  the  actual  process  has  not  been 
observed,  it  is  reasonable  to  assume  that  the  mesoderm  is  here  also  a  derivative 
of  the  "primitive  intestinal  cord,"  and  since  the  latter  is  produced  by  the  in- 
vagination  (gastrulation,  see  p.  62)  and  consists  of  protentoderm,  the  gastral 


GERM  LAYERS. 


79 


mesoderm  is  a  derivative  of  the  protentoderm  or  invaginated  cells.     Also,  as  the 
invagination  is  a  continuous  process  from  the  first  formation  of  the  crescentic 


Ectoderm 


Neural 
tube 


Entoderm 


Ccfclom 


FIG.  72. — Transverse  section  of  chick  embryo  (2  days  incubation).    Photograph. 
The   parietal  mesoderm   (lying  above  the  ccelom)   is  not   labeled.     The  two  large  vessels  under 
the  primitive  segments  are  the  primitive  aortae.     Spaces  separating  germ  layers  are  due  to 

shrinkage. 

groove  up  through  the  formation  of  the  ''primitive  intestinal  cord"  (see  p.  62), 
one  can  readily  understand  how  the  mesoderm  is  first  formed  in  the  line  of  the 
primitive  groove  and  continues  to  be  formed  progressively  forward  as  the  invagi- 


Area  pellucida 
Area  vasculosa 


Head  fold 
Neural  groove 

Primitive  segment 
Primitive  groove 


FIG.  73. — Dorsal  view  of  duck  embryo,  with  two  pairs  of  primitive  segments.     Bonnet. 

nation  pushes  farther  and  farther  forward  to  form  the  "primitive  intestinal 
cord."  The  gastral  mesoderm  is  thus  from  its  beginning  continuous  with  the 
peristomal  mesoderm,  the  two  together  forming  a  single  plate  of  cells. 


80 


TEXT-BOOK  OF  EMBRYOLOGY. 


As  described  above,  the  mesoderm  of  the  chick  is  at  first  a  solid  plate  of  cells. 
The  cavity  in  the  mesoderm — the  ccelom — appears  as  the  result  of  a  splitting 
of  the  originally  solid  mesoderm  layer  into  two  sublayers — the  parietal  and  the 
visceral  (Fig.  72).  At  the  same  time  that  portion  of  the  mesoderm  which  lies 
adjacent  to  the  neural  groove  on  both  sides  of  the  medial  line  becomes  differen- 
tiated into  two  series  of  bilaterally  symmetrical  segments — the  primitive  seg- 
ments, which  are  connected  with  one  another  by  intermediate  thinner  parts 
(Figs.  73,  74  and  72).  The  splitting  of  the  mesoderm  to  form  the  ccelom  begins 
some  distance  from  the  medial  line  and  progresses  both  laterally  and  medially. 


Neuropore 


Fore-brain  vesicle 


Head  fold 


Proamnion 


Mid-  and  hind- 
brain  vesicles 


Edge  of 
blastoderm 


Neural  fold 


Primitive 
groove 


FIG.  74.— Dorsal  view  of  chick  embryo  with  ten  pairs  of  primitive  segments.     Bonnet. 


The  ccelom  does  not,  however,  reach  the  primitive  segments,  for  a  small  solid 
mass  of  cells— the  intermediate  cell  mass  (Fig.  81)— always  intervenes  between 
the  ccelom  and  the  segments.  Furthermore,  the  ccelom  from  the  beginning 
shows  no  segmentation. 

The  formation  of  the  neural  groove  and  neural  tube  from  the  ectoderm  and 
the  separation  of  the  chorda  anlage  from  the  entoderm  are  much  the  same  as  in 
the  frog.  A  decided  difference  is,  however,  to  be  noted  in  the  shape  of  the 
chick's  blastoderm.  Since  in  this  case  the  yolk  plays  but  a  small  part  in  seg- 
mentation, the  germ  layers  at  first  lie  flat  upon  the  surface  of  the  yolk,  the 


GERM  LAYERS. 


81 


archenteron  being  a  flat  cavity  between  the  entoderm  and  the  yolk  (Figs.  67,  68 
and  69) .  The  tubular  form  of  the  intestine  is  brought  about  later  in  connection 
with  the  constriction  of  the  embryo  from  the  yolk  sac  (p.  136;  see  also  forma- 
tion of  primitive  gut,  p.  316). 

Mesoderm  Formation  in  Mammals. — In  Mammals  the  same  difficulties 
are  met  with  in  determining  the  origin  of  the  mesoderm  as  in  the  chick.  At  the 
same  time,  transverse  sections  through  the  developing  mammalian  blastoderm 


Si 


Mesoderm 


Yolk          Completion 
entoderm  plate 


Pr.int.co. 

P.gr.  Ectoderm 

I 


Yolk  entoderm  Pr.st. 

FIG.  75. — Transverse  sections  of  embryonic  disk  of  dog.     Bonnet. 

Sections  of  disk  shown  in  Fig.  53.  Letters  and  numbers  at  right  (Sj-S^  indicate  plane  of  sections 
in  Fig.  53.  P.gr.,  Primitive  groove;  Pr.int.co.,  primitive  intestinal  cord;  Pr.st.,  all  three 
germ  layers  fused  in  primitive  streak. 

at  different  stages  show  conditions  which  bear  much  resemblance  to  those  in  the 
chick,  and  lead  toward  the  conclusion  that  the  processes  in  the  two  cases  are 
much  alike. 

Referring  back  to  gastrulation,  it  will  be  remembered  that  on  surface  view 
the  germ  disks  of  the  chick  and  of  the  dog  were  very  similar  (compare  Fig.  46 
with  Fig.  53,  and  Fig.  50  with  Fig.  54,  a).  After  the  formation  of  the  primitive 
streak  in  the  dog,  sections  through  this  region  show  the  mesoderm  interposed 
between  the  ectoderm  and  entoderm  (here  yolk  entoderm)  and  all  three  germ 


82 


TEXT-BOOK  OF  EMBRYOLOGY. 


layers  fused  beneath  the  primitive  groove  (Fig.  75,  S3  and(S4;  compare  with 
Fig.  66).  The  origin  of  the  mesoderm  is  probably,  as  in  the  chick,  to  be  at- 
tributed to  the  invaginated  cells  (protentoderm)  along  the  line  of  the  primitive 
groove.  The  mesodermal  cells  first  appear  as  a  small  mass  beneath  the  primi- 
tive groove  (Fig.  76,  a) ;  they  then  spread  out  laterally  between  the  ectoderm  and 
(yolk)  entoderm  (Fig.  76,  b).  Beneath  the  point  of  origin,  that  is,  along  the 


Primitive  streak    Entoderm      Mesoderm      Ectoderm 


FIG.  76. — Transverse  sections  of  embryonic  disks  of  rabbit,  (a)  Kdlliker,  (b)  Rabl. 
a,  section  through  primitive  streak  of  embryo  of  6  days  and  18  hours;  b,  section  through  Hensen's 
node  of  embryo  of  7  days  and  3  hours. 

line  of  the  primitive  groove,  they  finally  fuse  with  the  (yolk)  entoderm  (Figs. 
75,  S3  and  S4;  compare  Figs.  76,  a  and  b,  and  Figs.  75,  S3  and  S4  with  Figs.  69, 
70  and  66). 

In  the  region  of  the  head  process,  as  in  the  chick,  sections  show  at  first  the 
entoderm  and  mesoderm  fused  in  the  medial  line,  and  the  ectoderm  as  a  sepa- 
rate layer  (Fig.  77  and  Fig.  75,  S2).  The  entoderm  with  which  the  mesoderm  is 


Mesoderm       Notochord 


Ectoderm 


Entoderm 


FIG.  77. — Transverse  section  of  embryonic  disk  of  rabbit,    van  Beneden. 


fused  represents  the  invaginated  cells,  that  is,  the  protentoderm  ("primitive 
intestinal  cord");  and,  as  in  the  chick,  it  seems  reasonable  to  assume  that  the 
mesoderm  is  derived  from  the  "  primitive  intestinal  cord  "  (protentoderm)  and 
grows  out  laterally  between  the  ectoderm  and  entoderm  (compare  Fig.  75,  S2 
with  Fig.  67). 

A  little  later,  in  the  region  of  the  head  process,  the  mesoderm  on  each  side  is 


GERM  LAYERS. 


83 


found  to  be  separated  from  the  parent  tissue  ("primitive  intestinal  cord"),  and 
the  latter  now  represents  the  anlage  of  the  notochord  (compare  Fig.  72  with 
Fig.  78). 

On  the  ground  that  the  primitive  groove  is  the  blastopore,  the  mesoderm 
arising  in  that  region  is  the  peristomal  mesoderm;  that  arising  from  the 
"primitive  intestinal  cord'*  in  front  of  the  primitive  groove  is  the  gastral  meso- 


Mesoderm       Ectoderm       Neural  groove 


Yolk  entoderm  Chordal  plate 

FIG.  78. — Transverse  section  of  embryonic  disk  of  dog.     Bonnet. 
Section  taken  near  anterior  end  of  head  process. 

derm.  The  peristomal  and  gastral  portion  together  constitute  a  continuous 
plate  of  cells  interposed  between  the  ectoderm  and  entoderm,  which  has  been 
derived  from  the  invaginated  cells  of  the  protentoderm. 

In  a  few  Mammals  (sheep,  roe,  shrew),  mesoderm  has  been  seen  to  arise 
some  distance  from  the  primitive  streak  and  head  process  (Fig.  79).  This  has 
been  called  the  peripheral  mesoderm,  but  it  soon  unites  with  the  peristomal  and 
gastral. 

Embryonic  disk 
I 


Peripheral 
mesoderm 


Ectoderm 


Area  of 
nvagination 


Nuclei  of 
yolk  entoderm 


FIG.  79. — Surface  view  of  embryonic  disk  of  sheep.     Bonnet. 
Disk  is  at  that  stage  of  development  when  gastrulation  begins  (in  region  marked  area  of  imagination). 

Primarily,  the  mesoderm  is  a  solid  plate  of  cells  with  no  indication  of  a  body 
cavity  (ccelom).  A  little  later  the  mesoderm  splits  into  two  layers,  the  parietal 
and  the  visceral,  between  which  lies  the  ccelom  (Fig.  81).  The  splitting  does 
not  effect,  however,  the  mesoderm  which  lies  adjacent  to  the  neural  groove  on 
both  sides  of  the  medial  line,  for  this  portion  becomes  differentiated  into  two 
series  of  bilaterally  symmetrical  segments — the  primitive  segments  (Figs.  80  and 


84 


TEXT-BOOK  OF  EMBRYOLOGY. 

*" 


Prim,  pericard.  

cavity 

Anlage         / 
of  heart      * 


Tail  fold 
of  amnion 


Telencephalon 
Diencephalon 
Mesencephalon 

Metencephalon 
Myelencephalon 


Peripheral  limit 
of  coelom 


IK 

FIG.  80. — Dorsal  view  of  dog  embryo  with  ten  pairs  of  primitive  segments.     Bonnet, 


Prim.    Intermed 
seg.      cell  mass 


Parietal  and 
visceral  mesoderm 


Ectoderm 
(epidermis) 


Chordal       Prim, 
plate          aorta 


Ccelom         Entoderm       Blood  vessels 
81. — Transverse  section  of  dog  embryo  with  ten  pairs  of  primitive  segments.    Bonnet. 


GERM  LAYERS. 


85 


8r).  The  splitting  of  the  mesoderm  begins  some  distance  from  the  medial  line 
and  proceeds  both  laterally  and  medially,  but  does  not  extend  quite  to  the 
primitive  segments.  Thus  a  solid  plate  of  cells  still  remains  between  the  ccelom 
and  the  segments — the  intermediate  cell  mass  (Fig.  81).  The  ccelom  shows  no 
segmentation.  (Compare  Fig.  80  with  Fig.  74  and  Fig.  Si  with  Fig.  72.) 

The  formation  of  the  neural  groove  and  tube  from  the  ectoderm  and  the 
separation  of  the  chorda  from  the  entoderm  are  processes  quite  analogous  to  the 
development  of  those  same  structures  in  the  lower  forms. 

As  in  the  chick,  so  also  in  Mammals,  the  blastoderm  is  at  first  spread  out  flat, 
forming  the  roof,  so  to  speak,  of  the  yolk  sac.  At  a  later  period,  in  connection 
with  the  closure  of  the  gut  and  the  establishment  of  the  external  forms  of  the 
body,  the  blastoderm  assumes  a  tubular  shape  (see  p.  136). 

A  comparison  of  the  foregoing  description  of  the  formation  of  the  mesoderm 
in  Mammals  with  the  description  of  the  corresponding  processes  in  the  chick 
(p.  75)  shows  their  essential  similarity. 


Strand  of  mesoderm 
in  exocoelom 


Entoderm 
of  yolk  sac 


Mesoderm 
of  yolk  sac 


w&ii 


W§ 


' 'W     W 

^* 


Part  of  exocrelom 

Trophoderm 

Mesoderm  of  chorion 
Ectoderm  of  amnion 
Entoderm 
Amniotic  cavity 
Embryonic  ectoderm 
Mesoderm 
Yolk  cavity 

Mesoderm 


FIG.  82. — Section  through  human  chorion,  amnion,  embryonic  disk,  and  yolk  sac.    Peters. 

Compare  with  Fig.  83.  ' 

The  Germ  Layers  in  Man. 

Of  the  actual  formation  of  the  germ  layers  in  man,  practically  nothing  is 
known.  There  are  no  observations  on  the  segmentation  of  the  ovum,  the  first 
differentiation  of  cells,  or  the  origin  of  the  embryonic  disk  and  germ  layers. 
A  very  young  human  ovum,  described  by  Leopold,  does  not  show  any  structures 
which  can  be  interpreted  as  the  embryonic  disk  or  any  part  of  it.  Another 


86 


TEXT-BOOK  OF  EMBRYOLOGY. 


young  ovum  described  by  Peters  shows  all  three  germ  layers  and  the  flat  embry- 
onic disk.  Bryce  and  Teacher  have  recently  described  an  ovum,  the  youngest 
on  record,  in  which  all  three  germ  layers  are  formed  (see  Fig.  106;  cf.  Fig.  83). 
A  section  through  the  ovum  described  by  Peters  (Fig.  82)  shows  the  ectoderm 
as  a  flat  layer  of  stratified  or  pseudostratified  cells,  the  margin  of  which  is  re- 
flected dorsally  as  the  lining  of  thereof  of  the  amniotic  cavity  (compare  Fig.  52,  c). 
Beneath  the  ectoderm  is  a  layer  of  cells — the  mesoderm — which  is  continu- 


Coagulum 


Trophoderm 
| 


Uterine  epithelium 


•:?  ft /•j£»a£VflK 

^f)|Kv^:-5 


«•.•  !-.-:'V.VS      ,?;'   .-/^O  Yolk  sac 

^'^A.^xV^A- 

«-*  *  •«  **••**•*».         «*J«*          1.     1?     —   -    f  / 


Gland 


Decidua  basalis 


Blood 


FlG.  83. — Section  through  very  young  human  chorionic  vesicle  embedded  in  the 

uterine  mucosa.     Peters. 

The  vesicle  measured  2.4  x  1.8  mm.,  the  embryo  .19  mm.  Peters  reckoned  the  age  as  3  or  4  days, 
but  later  studies  of  other  embryos  go  to  show  that  the  age  is  much  greater;  Bryce  and 
Teacher  estimate  it  at  14  to  15  days. 

ous  at  its  margin  with  the  mesoderm  of  the  roof  of  the  amnion,  with  mesoderm 
lining  the  chorionic  vesicle,  and  also  with  the  mesoderm  covering  the  yolk  sac 
Fig.  83).  Beneath  the  mesoderm  of  the  embryonic  disk  is  a  layer  of  entoderm 
which  also  extends  ventrally  to  line  the  yolk  sac.  There  is  here  no  trace  of  an 
invaginated  entoderm  from  which  the  mesoderm  might  arise. 

Graf  Spee  has  described  an  ovum  somewhat  older  than  Peters',  in  which  the 
embryonic  disk  shows  certain  features  which  are  comparable  with  those  in 
lower  Mammals.  On  surface  view  (Fig.  84),  the  primitive  groove  is  especially 


GERM  LAYERS. 


87 


prominent  and  the  opening  at  its  anterior  end,  corresponding  to  Hensen's  node, 
is  usually  well  marked.  The  line  of  the  head  process  is  strongly  marked  by  a 
deep  groove — the  neural  groove  (compare  Fig.  84  with  Fig.  54,  a). 

A  longitudinal  section  in  the  medial  line  of  this  disk  (Fig.  85)  shows  a  re- 
markable similarity  to  a  corresponding  section  of  the  bat's  disk  (Fig.  55).  The 
ectoderm  consists  of  a  single  layer  of  columnar  cells  interrupted  only  at  the 
opening  of  the  blastopore  (anterior  end  of  the  primitive  groove).  The  entoderm 
(chorda  anlage)  also  consists  of  a  single  layer  of  cells  which  is  continuous  at  the 
blastopore  with  the  ectoderm.  In  the  region  of  the  primitive  groove  the  per- 


Yolk  sac 


A nun on 


Neural  groove 


Chorion 


FIG.  84. — Dorsal  view  of  human  embryo,  two  millimeters  in  length,  with  yolk  sac. 

von  Spee,  Kollmann. 
The  amnion  is  opened  dorsally. 


istomal  mesoderm  is  present.  The  embryonic  disk  forms  the  roof,  so  to  speak, 
of  the  yolk  sac. 

A  transverse  section  (Fig.  86)  through  the  primitive  groove  shows  all  three 
germ  layers  fused  in  the  medial  line,  but  separated  laterally.  In  this  case  there 
is  a  striking  resemblance  to  the  condition  seen  in  a  corresponding  section  of  the 
rabbit's  disk  (Fig.  87). 

Apart  from  the  embryonic  disk,  the  conditions  are  very  similar  to  those  in 
Peters'  ovum  (compare  Figs.  85  and  82). 

The  unusual  feature  in  both  these  embrvos  is  the  enormous  extent  of  the 


88 


TEXT-BOOK  OF  EMBRYOLOGY. 


mesoderm.     In  Graf  Spec's  ovum  both  longitudinal  and  transverse  sections 
would  suggest  the  same  origin  for  the  intraembryonic  mesoderm  as  in  lower 


Chorionic  villi 


Mesoderm 
of  yolk  sac 


Blood  vessel 


FIG.  85. — Medial  section  of  human  embryo  shown  in  Fig.  84.     von  Spee,  Kottmann. 

Mammals,  but  the  extent  of  the  extraembryonic  mesoderm,  at  this  early  stage 
of  the  embryonic  disk,  would  indicate  a  departure  from  the  conditions  seen  in 
the  lower  Mammals.  In  other  words,  it  scarcely  seems  possible  that  the 

Ecto- 
Mesoderm   derm    Primitive  groove 


^*\a  ^  .jj',3    -^f^p  <n<s£iis  ft       vt* 


Ectode 

Parietal  mesoderm 
Visceral  mesoderm 

Entoderm 
FIG.  86. — Transverse  section  through  primitive  streak  of  embryo  shown  in  Fig.  84.    von  Spee. 

mesoderm  which  lines  the  chorionic  vesicle  and  covers  the  yolk  sac  has  grown 
out  from  the  mesoderm  which  arises  within  the  embryonic  disk;  it  seems  more 


GERM  LAYERS. 


Parietal  mesodenn  Primitive  groove 

Visceral  mesoderm  I  Primitive  fold 


Entoderm 
FIG.  87. — Transverse  section  through  primitive  groove  of  rabbit  embryo,     -van  Beneden, 


D 


FIG.  88. — Diagrams  representing  hypothetical  stages  in  the  development  of  the  human  embryo. 

A,  Morula;  compare  with  Fig.  33,  a.  B,  Morula  with  differentiated  superficial  cells;  compare  with 
Fig-  33,  b.  C,  Central  cells  have  become  vacuolized  to  form  the  yolk  cavity,  leaving  a  small 
group  (the  inner  cell  mass)  attached  to  the  enveloping  layer  (trophoderm) ;  compare  with 
Fig.  33,  d.  D,  Cells  of  the  inner  cell  mass  which  are  adjacent  to  the  yolk  cavity  have  become 
differentiated  and  have  begun  to  grow  around  the  cavity,  forming  the  entoderm;  compare 
with  Fig.  52,  a. 


90 


TEXT-BOOK  OF  EMBRYOLOGY. 


reasonable  to  suppose  that  it  has  arisen  outside  the  embryonic  disk  and  united 
with  the  intraembryonic  mesoderm  secondarily. 

While  neither  the  origin  of  the  extraembryonic  mesoderm,  nor  its  behavior 
up  to  the  stage  in  Bryce  and  Teacher's  ovum,  has  been  observed  in  man,  it  is 
possible  to  construct  hypothetical  diagrams  which  allow  of  comparison  with 
what  actually  occurs  in  the  lower  Mammals.  The  morula,  the  differentiation 


-  /{trj  rji(ftic     Ca.vit 


V<  see  rat  __ 
Mesoderrrj 

Parietal_ 
Mesoder 


FIG.  89. — Diagrams  representing  hypothetical  stages  in  the  development  of  the 

human  embryo  (to  follow  Fig.  88). 

A,  Entoderm  surrounds  the  yolk  cavity;  part  of  the  cells  of  the  inner  cell  mass  have  become 
vacuolated,  thus  forming  the  amniotic  cavity,  while  the  remainder  constitute  the  embryonic 
ectoderm;  compare  with  Fig.  52.  B,  Mesoderm  (represented  by  dotted  portion)  has  appeared 
between  the  entoderm  and  trophoderm,  between  the  entoderm  and  ectoderm  of  the  embryonic 
disk,  and  in  the  roof  of  the  amnion.  C,  The  mesoderm  around  the  yolk  cavity  has  split  into 
a  parietal  and  a  visceral  layer,  the  cleft  between  being  the  anlage  of  the  extraembryonic 
body  cavity  (exoccelom). 

of  the  superficial  layer  of  cells,  the  formation  of  the  trophoderm  and  inner  cell 
mass,  and  the  differentiation  of  the  primary  entoderm  may  be  represented 
hypothetically  by  the  diagrams  in  Fig.  88.  These  are  quite  comparable  with 
the  corresponding  stages  of  development  in  the  bat  (Fig.  33).  In  Fig.  89,  A, 
the  amniotic  cavity  formed  by  a  vacuolization  of  a  part  of  the  inner  cell  mass  is 
shown,  and  also  the  entoderm  lining  the  entire  yolk  cavity.  This  is  also  com- 


GERM  LAYERS. 


91 


parable  with  conditions  in  the  bat  (Fig.  52).  In  the  next  stage  (Fig.  89,  B) 
the  mesoderm  is  present  all  the  way  around  between  the  trophoderm  and  ento- 
derm, in  the  roof  of  the  amniotic  cavity,  and  between  the  ectoderm  and  entoderm 
in  the  embryonic  disk.  It  is  possible  that  the  mesoderm  arises  in  situ  as  a  deriv- 
ative of  the  entoderm  or  trophoderm.  Since  in  the  lower  Mammals  it  arises 
from  entoderm,  a  similar  origin  here  seems  the  more  reasonable. 


FIG.  90. — Diagrams  representing  stages  of  development  of  the  human  embryo  (to  follow  Fig.  89). 
At  A  stage  that  corresponds  approximately  to  those  of  Peters'  and  Bryce-Teacher's  embryos  (Figs. 
83  and  107).  Owing  to  the  rapid  enlargement  of  the  chorionic  vesicle,  the  exfraembryonic 
body  cavity  has  become  much  larger  than  in  Fig.  89,  C.  B,  A  stage  (in  longitudinal  section) 
corresponding  to  that  of  von  Spec's  embryo  (Fig.  85).  Only  a  part  of  the  chorion  is  shown; 
the  embryonic  disk  is  slightly  constricted  from  the  yolk  sac;  note  the  belly  stalk,  comparing 
with  A.  C,  Transverse  section,  same  stage  as  B.  D,  Longitudinal  section,  stage  somewhat 
later  than  B.  Note  the  greater  degree  of  constriction  between  the  embryo  and  yolk  sac,  and 
the  larger  amnion. 


In  the  majority  of  the  lower  Mammals  the  intraembryonic  mesoderm  arises 
from  the  entoderm  and  then  grows  out  into  the  wall  of  the  blastodermic  vesicle. 
In  a  few,  however  (sheep,  roe,  shrew),  the  peripheral  mesoderm  (p.  83) 
arises  outside  of  the  embryonic  disk  and  unites  with  the  intraembryonic  meso- 
derm secondarily.  It  might  be  suggested  that  the  formation  of  peripheral 


92  TEXT-BOOK  OF  EMBRYOLOGY. 

mesoderm  outside  of  the  embryonic  disk  is  an  intermediate  step  between  the 
formation  of  mesoderm  entirely  within  the  embryonic  disk  and  its  formation 
around  the  entire  vesicle,  as  in  the  hypothetical  case. 

Neither  in  Peters'  nor  in  Graf  Spec's  ovum  is  any  embryonic  body  cavity 
present.  But  in  both  cases  a  very  large  cavity  exists  between  the  mesoderm  of 
the  yolk  sac  and  that  of  the  chorion.  This  cavity — the  extraembryonic  body 
cavity  (exocodom)  — probably  arises  by  a  splitting  of  the  extraembryonic  meso- 
derm into  two  layers,  parietal  and  visceral,  just  as  the  embryonic  body  cavity  in 
other  Mammals  is  the  result  of  a  splitting  of  the  intraembryonic  mesoderm 
(p.  83).  The  splitting  would  occur  as  shown  in  Fig.  89,  C.  The  parietal 
layer  which  with  the  trophoderm  becomes  the  chorion,  then  grows  rapidly  and 
becomes  widely  separated  from  the  visceral  layer,  the  latter  with  the  entoderm 
constituting  the  wall  of  the  yolk  sac.  Thus  a  stage  is  reached  which  is  shown  in 
Fig.  89,  C,  and  which  corresponds  with  Peters'  ovum  (Fig.  83).  The  embry- 
onic disk  with  its  yolk  sac  and  amniotic  cavity  occupies  but  a  small  space  within 
the  chorionic  vesicle.  Consult  also  Fig.  106,  showing  the  Bryce-Teacher  ovum. 

The  stage  corresponding  to  Graf  Spec's  ovum  would  be  produced  by  a  fur- 
ther splitting  of  the  mesoderm  in  the  roof  of  the  amnion,  so  that  finally  the  em- 
bryonic disk  and  yolk  sac  remain  attached  to  the  chorion  only  by  a  band  of 
mesoderm,  the  belly  stalk  (Fig.  90;  compare  with  Fig.  85). 

Even  at  this  stage,  no  body  cavity  is  present  within  the  embryonic  disk 
(Fig.  86).  When  it  does  appear,  however,  it  becomes  continuous  laterally  with 
the  exoccelom  (see  Chap.  XIV),  and  the  parietal  and  visceral  layers  of  meso- 
derm within  the  embryonic  body  are  continuous,  respectively,  with  the  parietal 
and  visceral  extraembryonic  mesoderm. 

References  for  Further  Study. 

ASSHETON,  R.:  The  Reinvestigation  into  the  Early  Stages  of  the  Development  of  the 
Rabbit.  Quart.  Jour,  of  Mic.  Sci.,  Vol.  XXXVII,  1894. 

ASSHETON,  R.:  The  Segmentation  of  the  Ovum  of  the  Sheep,  with  Observations  on  the 
Hypothesis  of  a  Hypoblastic  Origin  for  the  Trophoblast.  Quart.  Jour,  of  Mic.  Sci.,  Vol. 
XLI,  1898. 

VAN  BENEDEN,  E.:  Recherches  sur  les  premiers  stades  du  developpement  du  Murin 
(Vespertilio  murinus).  Anat.  Am.,  Bd.  XVI,  1899. 

BONNET,  R.:  Lehrbuch  der  Entwicklungsgeschichte.     Berlin,  1907. 

BONNET,  R.:  Beitrage  zur  Embryologie  der  Wiederkauer  gewonnen  aus  Schafei.  Arch. 
/.  Anat.  u.  Physiol.,  Anat.  Abth.,  1884,  1889. 

BONNET,  R.:  Beitrage  zur  Embryologie  des  Hundes.  Anat.  Hefte,  Bd.  IX,  1897;  Bd. 
XVI,  1901. 

BRYCE,  T.  H.,and  TEACHER,  J.  H.:  Early  Development  and  Imbedding  of  the  Human 
Ovum.  Glasgow,  1908. 

HARPER,  E.  H.:  The  Fertilization  and  Early  Development  of  the  Pigeon's  Egg.  Am. 
Jour,  of  Anat.,  Vol.  Ill,  1904. 

HARTMAN,  C.  G.:  Studies  in  the  Development  of  the  Opossum.  Jour,  of  Morph.,  Vol. 
XXVII,  1916. 


GERM  LAYERS.  93 

HATSCHEK,  B.:  Studien  iiber  Entwicklung  des  Amphioxus.  Arbeiten  aus  dem  zool. 
Instil,  zu  Wien,  Bd.  IV,  1881. 

HEAPE,  W.:  The  Development  of  the  Mole  (Talpa  europaea).  Quart.  Jour,  ofMic.  Sci., 
Vol.  XXIII,  1883. 

HERTWIG,  O.:  Die  Lehre  von  den  Keimblattern.  In  Hertwig's  Handbuch  der  vergleich. 
u.  experiment.  Entwickehingslehre  der  IVirbeltiere,  Bd.  I,  Teil  I,  1903. 

HUBER,  G.  CARL:  The  Development  of  the  Albino  Rat.  Memoirs  of  the  Wistar  Insti- 
tute, Xo.  5,  1915. 

HUBRECHT,  A.  A.  W.:  Studies  on  Mammalian  Embryology.  II:  The  Development  of 
the  Germinal  Layers  of  Sorex  vulgaris.  Quart.  Jour,  of  Mic.  Sci.,  Vol.  XXXI,  1890. 

LILLIE,  F.  R.:  The  Development  of  the  Chick.     New  York,  1908. 

McMuRRiCH,  J.  P.:  The  Development  of  the  Human  Body.     Philadelphia,  1907. 

MINOT,  C.  S.:  Laboratory  Text -book  of  Embryology.     Philadelphia,  1903. 

MORGAN,  T.  H.:  The  Development  of  the  Frog's  Egg.     New  York,  1897. 

MORGAN,  T.  H.,  and  HAZEN,  A.  P.:  The  Gastrulation  of  Amphioxus.  Jour,  of  Morphol. t 
Vol.  XYL  1900. 

PATTERSON,  J.  T.:  On  Gastrulation  and  the  Origin  of  the  Primitive  Streak  in  the 
Pigeon's  Egg.  Biolog.  Bull.,  Vol.  XIII,  1907. 

PEEBLES,  F.:  The  Location  of  the  Chick  Embryo  upon  the  Blastoderm.  Jour,  of  Ex- 
periment. Zool.,  Vol.  I,  1904. 

PETERS,  H.:  Ueber  die  Einbettung  des  menschlichen  Eies  und  das  fruheste  bisher  be- 
kannte  menschliche  Placentationstadium.  Leipzig  u.  Wien,  1899. 

YON  SPEE,  GRAP:  Beobachtungen  an  einer  menschlichen  Keimscheibe  mit  offener  Medul- 
larrinne  und  Canalis  neurentericus,  Arch.  f.  Anat.  u.  Physiol.,  Anal.  Abth.,  1889. 

SOBOTTA,  J.:  Die  Entwickelung  des  Eies  der  Maus  vom  Schluss  der  Furchungsperiode 
bis  zum  Auftreten  der  Amnionfalte.  Arch.  f.  mik.  Anat.,  Bd.  LXI,  1902. 

WILSON,  E.  B.:  Amphioxus  and  the  Mosaic  Theory  of  Development.  Jour,  of  Morphol., 
Vol.  VIII,  1893. 


CHAPTER  VII. 
FCETAL  MEMBRANES. 

In  all  Vertebrates,  with  the  exception  of  Fishes  and  Amphibians  which  lay 
their  eggs  in  water,  there  begin  to  develop  at  a  very  early  stage  certain  accessory 
or  extraembryonic  structures  which  may  be  conveniently  called  fatal  mem- 
branes. The  development  of  these  structures  is  very  closely  related  to  the  de- 
velopment of  the  embryo  itself,  and  their  presence  is  apparently  largely  depend- 
ent upon  the  very  considerable  length  of  embryonic  life  in  these  forms,  during 
which  it  is  necessary  for  the  embryo  to  maintain  a  definite  relation  to  its  food 
supply  and  to  possess  means  of  discharging  waste  products.  The  fcetal  mem- 
branes, therefore,  have  to  do  with  the  protection  and  nutrition  of  the  growing 
embryo  and  also  are  connected  with  the  care  of  the  wraste  products  of  fcetal 
metabolism. 

Under  the  head  of  fcetal  membranes  are  to  be  considered  (i)  the  amnion, 
(2)  the  allantois,  (3)  the  chorion;  also  in  connection  with  these,  the  yolk  sac  and 
the  umbilical  cord. 

The  development  of  these  structures  in  Mammals  and  especially  in  man  is 
extremely  complex  and  can  be  best  understood  by  comparison  with  their  simpler 
development  in  Reptiles  and  Birds. 

FCETAL  MEMBRANES  IN  BIRDS  AND  REPTILES. 

Throughout  these  two  classes  there  is  such  uniformity  in  the  formation  of 
the  fcetal  membranes  that  the  chick  may  be  taken  as  typical.  The  chief 
characteristic  of  these  classes,  as  influencing  the  form  and  structure  of  the  fcetal 
membranes,  is  the  very  large  amount  of  yolk  stored  up  within  the  egg  for  the 
nutrition  of  the  embryo.  This  is  made  necessary  by  the  early  separation  of  the 
egg  from  the  mother,  in  contrast  to  the  close  nutritional  relationship  between 
mother  and  foetus  which  obtains  in  Mammals  (excepting  Monotremes) ,  where 
the  young  are  retained  within  the  body  of  the  mother  up  to  a  comparatively  late 
developmental  stage. 

The  Amnion. — Returning  to  that  point  in  the  development  of  the  blastoderm 
of  the  chick  where  no  trace  of  amnion  has  as  yet  appeared,  we  recall  that  the 
blastoderm  at  this  stage  consists  of  three  layers,  ectoderm,  mesoderm  and 
entoderm;  that  the  medial  line  of  the  embryo  is  marked  by  the  neural  groove, 
flanked  by  the  neural  folds  which  are  continuous  with  each  other  anteriorly;  that 

95 


96 


TEXT-BOOK  OF  EMBRYOLOGY. 


on  each  side  of  the  neural  groove  between  ectoderm  and  entoderm  the  mesoderm 
is  a  solid  mass  of  cells,  while  more  laterally  the  mesoderm  is  split,  its  peripheral 
layer  with  the  adjacent  ectoderm  forming  the  somatopleure,  its  central  layer 
with  the  adjacent  entoderm  forming  the  splanchnopleure;  that  between  soma- 
topleure and  splanchnopleure  is  the  body  cavity.  Ventral  to  the  neural  groove 
is  the  notochord,  while  ventral  to  the  latter  is  the  primitive  gut,  the  roof  of  which 
is  formed  of  entoderm  (Fig.  72). 

The  first  indication  of  amnion  formation  is  the  appearance  of  a  fold — the 
head  amniotic  fold — just  in  front  of  the  anterior  union  of  the  neural  folds  (Figs. 


ar.  op.1 
ed.  mes. 
h.  am.  f. 


pr.  seg. 


ar.  op.2 


ar.  pel. 


FIG.  91. — Dorsal  view  of  embryo  of  bird  (Phaeton  rubricauda)  with  fifteen  pairs  of 

primitive  segments.     Schauinsland. 

ar.  op.1,  Area  opaca,  portion  in  which  mesoderm  is  not  yet  present;  ar.  op.2,  area  opaca;  ar.  pel., 
area  pellucida;  cce.,  bladder-like  dilatation  of  ccelom;  ed.  mes.,  edge  of  mesoderm;  h.  am.  }., 
head  amniotic  fold;  pr.  seg.,  primitive  segments;  x,  portion  of  amniotic  fold  containing  no 
mesoderm. 


91  and  97,  b).  This  occurs  during  the  second  day  of  incubation0  After  the  head 
fold  has  become  well  developed  and  extends  back  over  the  embryo  like  a  hood 
(Fig.  93),  similar  lateral  and  tail  folds  make  their  appearance  (Figs.  92  and  97, 
a  and  b).  The  folds  continue  to  grow  over  the  dorsum  of  the  embryo  and 
finally  meet  and  fuse  in  the  mid-dorsal  line,  forming  the  amniotic  suture  (Fig.  94). 
The  amniotic  folds  from  the  beginning  involve  the  somatopleure,  that  is, 
the  ectoderm  and  parietal  mesoderm.  But  since  they  arise  some  distance  from 
the  developing  embryonic  body,  the  extraembryonic  portions  only  are  involved. 
At  the  same  time  a  portion  of  the  extraembryonic  body  cavity  is  also  carried 
dorsally  within  the  folds  (Figs.  92  and  95).  When  the  folds  unite  over  the 


FCETAL  MEMBRANES. 


97 


embryo  they  break  through  at  the  line  of  contact,  thus  leaving  the  outer  layers 
of  the  folds  continuous  and  the  inner  layers  continuous,  with  the  extraembryonic 
body  cavity  continuous  between  the  outer  and  inner  layers. 


n.  tu. 


t.  am.  f. 


ect. 


pr.  g. 


ent. 


1    !  i    i    i     i 

mes.   b.c.  al.    a.m.  e.g.       ta. 


FIG.  92. — Medial  section  of  caudal  end  of  chick  embryo  (at  end  of  second 

day  of  incubation).     Duval. 

a/.,  Beginning  of  allantoic  evagination;  a.m.,  anal  membrane;  b.c.,  extraembryonic  body  cavity; 
e.g.,  caudal  gut;  ect.,  ectoderm;  ent.,  entoderm;  mes.,  mesoderm;  mes.1,  parietal  mesoderm; 
mes.2,  visceral  mesoderm;  n.  tu.y  neural  tube;  pr.  g.,  primitive  gut;  t.  am.  /.,  tail  amniotic 
fold;  ta.,  tail. 

The  result  of  the  development  of  the  amniotic  folds  is : — 
i.  That  the  embryo  is  completely  enclosed  dorsally  and  laterally  by  a  cavity, 
the  amniotic  cavity,  which  is  lined  by  ectoderm  continuous  with  the  ectoderm- 


Area 

opaca 

Edge  of 
mesoderm 


Dorsal  amniotic 
suture 


Primitive 
streak 


FIG.  93. — Dorsal  view  of  embryo  of  albatross,  showing  amnion  covering  cephalic 

end  of  embryo.     Schaninsland. 
x,  Portion  of  blastoderm  containing  no  mesoderm. 

later  epidermis — of  the  embryo,  the  ectoderm  lining  the  cavity  and  the  overlying 
parietal  mesoderm  together  constituting  the  amnion  (Fig.  96). 

2.  That  the  outer  parts  of  the  amniotic  folds  become  completely  separated 


TEXT-BOOK  OF  EMBRYOLOGY. 


from  the  inner — the  amnion — to  form  a  second  membrane  consisting  externally 
of  ectoderm,  internally  of  mesoderm  and  called  at  first  the  serosa  or  jalse 
amnion,  later  the  primitive  chorion  (Fig.  96). 

3.  That  the  extraembryonic  body  cavity  unites  across  the  medial  line 
dorsally,  thus  separating  the  amnion  from  the  primitive  chorion  (Fig.  97,  a,  b 
and  c). 

During  the  formation  of  the  amnion  the  chick  embryo  is  becoming  more  and 
more  definitely  constricted  off  from  the  underlying  large  yolk  mass  which  is 
liquefying  and  into  which  the  embryo  sinks  somewhat.  At  the  same  time  the 


Ant.  vitelline  vein    Mesoderm 


Omphalomesenteric 
(vitelline)  vein 


Primitive  streak 


Area  opaca 
Sinus  terminalis 

Extraembryonic  body  cavity 

Amnion 
Amniotic  suture 


Area  pellucida 


Amniotic  suture 
^Lateral  amniotic  fold 


Tail  amniotic  fold 
Area  opaca 


FIG.  94. — Dorsal  view  of  embryo  of  albatross,  showing  amnion  covering  greater 
part  of  embryo.     Schauinsland. 

amniotic  cavity  continues  to  increase  in  size  and  extends  also  ventrally  beneath 
the  embryo  so  that  the  embryo  is  everywhere  enclosed  within  the  amnion 
except  at  its  narrow  connection  with  the  yolk  (Fig.  97,  c,  d). 

The  amniotic  cavity  is  filled  with  fluid,  the  liquor  amnii,  the  origin  of  which 
is  uncertain.  In  it  the  embryo  floats  freely,  attached  only  by  its  ventral  con- 
nection with  the  yolk.  At  about  the  fifth  day  of  incubation  rhythmical  con- 
tractions of  the  amnion  begin.  These  are  apparently  due  to  the  development 
of  contractile  fibers  in  its  mesodermic  tissue  and  give  to  the  embryo  a  regular 
oscillating  motion. 


FCETAL  MEMBRANES. 


99 


The  Yolk  Sac. — The  simplest  type  of  yolk  sac  is  found  in  Amphibians  and 
Fishes.     In  Amphibians  the  yolk  is  enclosed  within  the  embryo,  the  cells  form- 


—  p.  mes. 


ent. 


pc.  ep, 


FIG.  95. — Transverse  section  of  embryo  of  albatross.     Schauinsland. 

Section  taken  through  region  of  heart,  am.,  amnion;  ao.,  aorta;  a.  v.v.,  anterior  vitelline  veins; 
ect.,  ectoderm;  ent.,  entoderm;  ep.,  epicardium;  ex.  b.  c.,  extraembryonic  body  cavity;  ht.,  heart; 
/. am./.,  lateral  amniotic  fold;  pc.,  pericardium;  ph.,  pharynx;  p.  mes.,  parietal  mesoderm; 
ser..  serosa  (chorion);  v.  mes.,  visceral  mesoderm;  *  point  at  which  extraembryonic  body 
cavity  passes  over  into  the  intraembryonic  (or  ccelom  proper). 

ing  a  part  of  the  intestinal  wall.     The  superficial  cells  are  split  off  to  form  the 
yolk  entoderm.     Investing  the  yolk  entoderm  is  the  visceral  mesoderm  which 


am.  sut. 


ect. 


— p.  mes. 


• —  v.  mes. 


it 


p.  pc. 

ht.      ph.  p.  pc. 

FIG.  96. — Transverse  section  of  embryo  of  albatross.     Schauinsland. 

Section  taken  through  region  of  heart,  am.,  Amnion;  am. sut.,  amniotic  suture;  a. v.v.,  anterior 
vitelline  veins;  ect.,  ectoderm;  ent.,  entoderm;  ex.  b.  c.,  extraembryonic  body  cavity;  ht.,  heart; 
p.  pc.,  primitive  pericardial  cavity;  ph.,  pharynx;  p. mes.,  parietal  mesoderm;  ser.,  serosa 
(chorion);  v. mes.,  visceral  mesoderm;  *  point  at  which  extraembryonic  body  cavity  passes 
over  into  intraembryonic  (or  ccelom). 

is  separated  from  the  parietal  mesoderm  by  the  body  cavity.     Outside  of  the 
parietal  mesoderm  is  the  ectoderm  (Fig.  65).     In  many  of  the  Fishes  the  germ 


100 


TEXT-BOOK  OF  EMBRYOLOGY. 


disk,  as  in  Reptiles  and  Birds,  is  confined  to  one  pole  of  the  egg.  Thus  in  these 
forms  the  embryonic  body  develops  on  the  surface  of  the  large  yolk  mass.  As 
the  embryo  develops  the  germ  layers  simply  grow  around  the  yolk  and  suspend 
it  from  the  ventral  side  of  the  embryo.  At  the  same  time  a  constriction  appears 
between  the  embryo  and  the  yolk  mass,  thus  forming  the  yolk  stalk.  In  this 
case  the  yolk  is  surrounded  from  within  outward,  by  entoderm,  visceral  and 


h.  am.  f. 


y.s. 


z.  g 


FIG.  97. — Diagrams  representing  stages  in  the  development  of  the  foetal  membranes 

in  the  chick.     Hertiing. 

i,  Transverse  section;  b,  c,  d,  longitudinal  sections;  yolk  represented  by  vertical  lines,  al.,  Allantois; 
aw.,  amnion;  am.  c.,  amniotic  cavity;  cce.,  ccelom;  dh.,  vitel line  area  between  two  dotted  lines 
which  represent  the  edge  of  the  mesoderm  (at  s.  t.)  and  entoderm  (at  z.£.);  dg.,  yolk  stalk; 
ds.,  yolk  sac;  d.  umb.,  dermal  umbilicus;  ect.,  ectoderm;  ent.,  entoderm;  ex.  b.  c.,  extraem- 
bryonic  body  cavity;  gh.,  area  vasculosa;  h.am.f.,  head  amniotic  fold;  m.,  mouth;  p.mes., 
parietal  mesoderm;  s.  /.,  sinus  terminalis;  ser.,  serosa  (chorion);  t.am.f.,  tail  amniotic  fold; 
umb.,  umbilicus;  r  mes.,  visceral  mesoderm;  z.  g.,  dotted  line  represents  edge  of  entoderm. 


parietal  mesoderm,  and  ectoderm  (Fig.  98).  The  yolk  furnishes  nutriment  for 
the  embryo.  This  is  conveyed  to  the  tissues  by  means  of  blood  vessels. 
Branches  of  the  vitelline  artery  ramify  in  the  wall  of  the  yolk  sac  (in  the  meso- 
dermal  tissue) ;  the  branches  converge  to  form  the  vitelline  veins  which  carry  the 
blood  back  to  the  embryo. 

In  the  chick,  while  the  amnion  is  forming,  the  inner  germ  layer  gradually 
extends  farther  and  farther  around  the  yolk  (Fig.  97,  a,  b,  c  and  d).     At  the 


FCETAL  MEMBRANES.  101 

same  time,  as  already  noted  (p.  98),  the  growth  of  the  amnion  ventrally  results 
in  a  sharp  constriction  which  separates  the  embryo  from  the  underlying  yolk. 
This  constriction  is  emphasized  by  constant  lengthwise  growth  of  the  embryo. 
Following  the  gradual  growth  of  the  entoderm  around  the  yolk,  the  mesoderm 
also  gradually  extends  around,  at  the  same  time  splitting  into  visceral  and 
parietal  layers,  so  that  the  entoderm  is  closely  invested  by  visceral  mesoderm 
(Fig.  97,  a,  b,  c  and  d).  Finally,  both  entoderm  and  mesoderm  enclose  com- 
pletely the  mass  of  yolk.  The  yolk  thus  becomes  enclosed  hi  the  yolk  sac 
which  consists  of  two  layers,  entoderm  and  visceral  mesoderm.  The  constricted 
connection  between  the  yolk  sac  and  the  embryo  is  the  yolk  stalk.  It  is  seen  by 
reference  to  the  diagrams  (Fig.  97)  that  the  entoderm  lining  the  yolk  sac  is 


FIG.  98. — Diagrammatic  longitudinal  section  of  selachian  embryo.     Hertwig. 

a.,  Anus;  d.,  yolk  sac;  dn.,  intestinal  umbilicus;  ds.,  visceral  layer  of  yolk  sac;  hs.,  parietal  layer  of 
yolk  sac;  hn.,  dermal  umbilicus;  2k1,  coelom;  lh2,  exoccelom;  m.,  mouth;  St.,  yolk  stalk. 


directly  continuous  through  the  yolk  stalk  with  the  entoderm  lining  the  primi- 
tive gut.  The  transition  line  between  extra-  and  intraembryonic  entoderm  is 
sometimes  referred  to  as  the  intestinal  umbilicus,  in  contradistinction  to  the  line 
of  union,  on  the  outside  of  the  yolk  stalk,  of  amniotic  and  embryonic  ecto- 
derm (the  latter  becoming  later  the  epidermis)  which  is  known  as  the  dermal 
umbilicus. 

As  in  Fishes  and  Amphibians,  so  also  in  Reptiles  and  Birds,  the  yolk  furnishes 
nourishment  for  the  growing  embryo,  and  is  conveyed  to  the  embryo  by 
the  blood.  At  a  very  early  stage  the  mesoderm  layer  of  the  yolk  sac  (visceral 
mesoderm)  becomes  extremely  vascular.  This  vascular  area  is  indicated  by  an 
irregularly  reticulated  appearance  in  the  periphery  of  the  blastoderm  and  is 
known  as  the  area  vasculosa  (Fig.  74).  The  area  vasculosa  increases  in  size  as 
the  mesoderm  grows  around  the  yolk  and  its  vessels  become  continuous  with 
those  in  the  embryo  (Fig.  212).  Some  of  these  vessels  enlarge  as  branches  of 
two  large  vessels  which  are  given  off  from  the  primitive  aortae,  the  mtelline  or 
omphalomesenteric  arteries.  (When  the  two  aortas  fuse  to  form  a  single 
vessel,  the  proximal  ends  of  the  vitelline  arteries  fuse  likewise.)  The  branches 
of  the  arteries  ramify  in  the  mesoderm  over  the  surface  of  the  yolk  and  then 


102  TEXT-BOOK  OF  EMBRYOLOGY. 

converge  to  form  other  vessels  which  enter  the  embryo  as  thevitellineoromphalo- 
mesenteric  veins  (Fig.  213).  As  the  mesoderm  extends  farther  and  farther 
around  the  yolk,  the  vessels  extend  likewise  until  the  entire  yolk  is  surrounded 
by  a  dense  plexus  of  blood  vessels  in  the  wall  of  the  yolk  sac. 

The  Allantois. — While  the  embryonic  intestine  is  first  assuming  the  form 
of  a  tube,  there  grows  out  ventrally  from  near  its  caudal  end,  during  the  third 
day  of  incubation,  a  diverticulum  which  is  the  beginning  of  the  allantois  (Fig. 
99).  This  increases  rapidly  in  size  and  pushes  out  into  the  extraembryonic 
body  cavity  behind  the  yolk  stalk.  As  it  is  a  diverticulum  from  the  intestine, 
it  consists  primarily  of  entoderm.  This  pushes  in  front  of  it,  however,  the 
splanchnic  (visceral)  mesoderm  which  becomes  the  outer  layer  of  the  membrane. 
The  connection  between  the  intestine  and  the  allantois  is  known  as  the  urachus. 
In  the  chick  the  allantois  attains  a  comparatively  large  size,  pushing  out  dorsally 


ex.b.c.  -' 

al.  p.  / 

al.  mes.  ent.         a.m.    e.g.    a.m. 

FIG.  99. — Longitudinal  section  of  caudal  end  of  chick  embryo  (end  of  third 

day  of  incubation).     Casser. 

al.,  Allantois;  al. p.,  allantois  prominence;  a.m.,  anal  membrane;  am.,  amnion;  am.  c.,  amniotic 
cavity;  e.g.,  caudal  gut;  cce.,  ccelom;  ect.,  ectoderm;  ent.,  entoderm;  ex.  b.  c.,  extraembryonic 
body  cavity;  mes.,  mesoderm;  pr.  g.,  primitive  gut;  t.,  tail. 

between  the  amnion  and  the  primitive  chorion  and  ventrally  between  the  latter 
and  the  yolk  sac  (Fig.  97,  b,  c  and  d).  The  inner  wall  of  the  allantoic  sac  blends 
with  the  amnion  about  the  seventh  day  of  incubation  and  with  the  yolk  sac  con- 
siderably later,  while  the  outer  wall  joins  the  primitive  chorion  to  form  the  true 
chorion,  or  as  it  is  sometimes  designated,  the  allanto-chorion  (see  p.  107).  As 
the  allantois  reaches  the  limit  of  the  yolk,  it  leaves  the  latter,  and  pushing  the 
primitive  chorion  before  it,  continues  around  close  under  the  shell  (Fig.  97) 
until  it  completely  encloses  the  albumen  at  the  small  end  of  the  egg. 
The  allantois  of  the  chick  performs  three  important  functions : 

1.  It  serves  as  a  receptacle  for  the  excretions  of  the  primitive  kidneys. 

2.  United  with  a  part  of  the  primitive  chorion  to  form  the  albumen  sac,  its 
vessels  take  up  the  albumen  as  nourishment  for  the  embryo.     Because  of  this 
function  and  also  because  of  the  fact  that  little  papillae  sometimes  appear  on  the 


FCETAL  MEMBRANES.  103 

inner  surface  of  the  albumen  sac,  evidently  for  the  purpose  of  increasing  its 
absorptive  surface,  this  albumen  sac  has  been  compared  by  some  to  a  placenta. 

3.  It  blends  with  the  primitive  chorion  to  form  the  true  chorion  and  being 
extremely  vascular  and  lying  just  beneath  the  porous  shell,  it  serves  as  the  most 
important  organ  of  fcetal  respiration. 

The  allantois  in  the  chick  is  an  extremely  vascular  organ,  the  network  of 
small  vessels  in  the  wall  being  composed  of  radicals  of  the  allantoic  or  umbilical 
vessels  of  the  embryo.  Soon  after  the  allantois  begins  to  develop,  two 
branches — the  umbilical  arteries — are  given  off  from  the  aorta  near  its  caudal 
end.  These  pass  ventrally  through  the  body  wall  of  the  embryo  and  thence 
out  via  the  umbilicus  to  break  up  into  extensive  networks  of  capillaries  in  the 
mesodermal  layer  of  the  allantois.  The  capillaries  converge  to  form  the  um- 
bilical veins  which  pass  into  the  embryo  via  the  umbilicus  and  thence  cephalad 
to  the  heart. 

During  the  incubation  period  of  the  chick  there  are  two  extraembryonic  sets 
of  blood  vessels.  One  set,  the  vitelline  (omphalomesenteric)  vessels  (p.  218), 
is  concerned  with  carrying  the  yolk  materials  to  the  growing  embryo.  The 
other  set,  the  umbilical  (allantoic)  vessels,  is  chiefly  concerned  with  respiration 
and  carrying  waste  products  to  the  allantois,  but  is  probably  in  part  concerned 
with  conveying  the  albumen  to  the  embryo.  When  the  chick  is  hatched,  and  the 
foetal  membranes  are  of  no  further  use  and  disappear,  the  extraembryonic  por- 
tions of  the  blood  vessels  also  disappear.  The  intraembryonic  portions  persist, 
in  part,  as  certain  vessels  in  the  adult  organism. 

The  Chorion  or  Serosa. — This  membrane  is  but  little  developed  in  the 
chick  as  compared  with  Mammals,  especially  the  Placentalia.  Its  mode  of 
origin  as  the  outer  leaves  of  the  amniotic  folds,  cut  off  from  the  amnion  by 
dorso-medial  extension  of  the  mesoderm  and  body  cavity,  has  been  described 
(P-  9?)-  It  consists,  as  there  shown,  of  extraembryonic  ectoderm  and  parietal 
mesoderm  (Fig.  96) .  As  first  formed  it  is  confined  to  the  immediate  region  of 
the  embryo  and  of  the  amnion  to  which  it  is  later  loosely  attached.  It  soon 
extends  ventrally  around  the  yolk  where  it  forms  what  is  sometimes  designated 
the  skin  layer  of  the  yolk  sac.  The  relation  of  the  outer  layers  of  the  allantois 
to  the  chorion  has  been  described  on  page  102,  and  is  illustrated  in  Fig.  99. 

FCETAL  MEMBRANES  IN  MAMMALS. 

The  development  of  the  fcetal  membranes  in  Mammals  presents  no  such 
uniformity  as  is  found  in  Birds  and  Reptiles  where  it  was  possible  to  describe 
their  formation  in  the  chick  as  typical  for  the  two  classes.  In  the  different 
Mammals  much  variation  occurs,  not  only  in  the  first  appearance  of  the  mem- 
branes but  also  in  their  further  development  and  ultimate  structure. 

In  some  forms  (rabbit,  for  example)  the  amnion  develops  in  a  manner  very 


104  TEXT-BOOK  OF  EMBRYOLOGY. 

similar  to  that  in  the  chick;  that  is,  by  a  dorsal  folding  of  the  somatopleure. 
There  is,  however,  no  head  fold  unless  a  temporary  structure  known  as  the 
proamnion  be  considered  as  such.  The  entire  rabbit  amnion  is  formed  by  an 
extension  over  the  embryo  of  the  tail  amniotic  fold.  In  other  forms  (bat  and 
probably  man)  the  amnion  and  amniotic  cavity  arise  in  situ  over  the  embryonic 
disk,  without  any  folding  of  the  somatopleure. 

Yolk  is  almost  entirely  lacking  in  most  Mammals,  but  the  yolk  sac  is  always 
present  although  it  soon  becomes  a  rudimentary  structure.  The  fact  that  the 
yolk  sac  is  always  present  points  toward  the  conclusion  that  Mammals  are 
descended  from  animals  which  possessed  large  ova  with  abundant  yolk.  As  a 
matter  of  fact  the  lowest  Mammals,  the  Monotremes,  possess  large  ova  with 
large  quantities  of  yolk.  These  are  deposited  by  the  female,  are  developed  in  a 
parchment-like  shell,  and  are  carried  about  in  the  brood-pouch. 

The  allantoic  sac  in  many  Mammals  is  a  very  rudimentary  structure  which, 
as  in  the  chick,  always  arises  as  an  evagination  from  the  caudal  end  of  the  gut. 
The  allantoic  blood  vessels,  however,  become  vastly  important  since  they  here 
not  only  carry  off  waste  products  from  the  embryo,  as  in  Reptiles  and  in  Birds, 
but  also  assume  the  function  of  conveying  nutriment  from  the  mother  to  the 
embryo.  In  assuming  this  new  function  they  are  no  longer  concerned  with 
the  allantoic  sac  proper  but  enter  into  a  new  relation  with  the  chorion. 

The  chorion  is  the  most  highly  modified  and  specialized  of  all  the  mam- 
malian foetal  membranes.  In  some  cases  (the  rabbit,  for  example)  it  arises  in 
connection  with  the  amnion,  as  in  the  chick,  by  a  dorsal  folding  of  the  somato- 
pleure. In  other  cases  (bat  and  probably  man)  it  arises  at  a  very  early  stage, 
partly  as  a  differentiation  of  the  superficial  layer  of  the  rnorula,  partly  as 
extraembryonic  parietal  mesoderm  which  develops  later.  In  all  cases  where 
the  embryo  is  retained  in  the  uterus  (except  Marsupials)  it  forms  a  most  highly 
specialized  and  complex  structure  which,  in  connection  with  the  allantoic 
vessels,  establishes  the  communication  between  the  mother  and  the  embryo. 

For  the  sake  of  clearness  it  seems  best  to  describe  first  the  earlier  stages  of 
the  foetal  membranes  in  some  case  where  the  development  resembles  that  of  the 
chick;  then  later  to  consider  the  more  specialized  types  of  development,  the 
ultimate  structure  of  the  membranes,  especially  the  chorion,  and  their  relation 
to  the  embryo  and  the  mother. 

Amnion,  Chorion,  Yolk  Sac,  Allantois,  Umbilical  Cord. — Referring 
back  to  the  mammalian  blastoderm  when  it  consists  of  the  three  germ  layers, 
it  will  be  remembered  that  the  embryonic  disk  forms  the  roof,  so  to  speak,  of  a 
large  cavity — the  yolk  cavity  or  cavity  of  the  blastodermic  vesicle  (Fig.  82) ; 
that  the  ectoderm  of  the  disk  is  continuous  with  a  layer  of  cells  which  extends 
around  the  vesicle — the  extraembryonic  ectoderm;  that  the  entoderm  of  the 
disk  is  continuous  with  the  entoderm  lining  the  cavity  of  the  vesicle;  that  the 


FCETAL  MEMBRANES. 


105 


mesoderm  extends  peripherally  beyond  the  disk  between  the  ectoderm  and 
entoderm  (Fig.  89) .  It  will  be  remembered  also  that  the  mesoderm  later  splits 
into  two  layers — the  parietal  and  visceral,  of  which  the  parietal  plus  the  ecto- 
derm forms  the  somatopleure  and  the  visceral  plus  the  entoderm  forms  the 


FIG.  ioo. — Diagrams  representing  six  stages  in  the  development  of  the  foetal  membranes 

in  a  mammal.     Modified  from  Kblliker. 

The  ectoderm  is  indicated  by  solid  black  lines;  the  entoderm  by  broken  lines;  the  mesoderm 

by  dotted  lines  and  areas. 

splanchnopleure;  and  that  the  cleft  between  the  two  layers  is  the  body  cavity 
or  coelom. 

In  further  development,  along  with  the  differentiation  of  the  embryonic 
body,  the  somatopleure  begins  to  fold  dorsally  at  a  short  distance  from  the 


106 


TEXT-BOOK  OF  EMBRYOLOGY. 


body  (Fig.  100,  2).  The  folds — amniotic  folds — appear  cranially,  laterally  and 
caudally.  These  folds  continue  to  grow  dorsally  (Fig.  100,  3)  and  finally  meet 
and  fuse  above  the  embryo  (Fig.  100,  4).  They  then  break  through  along  the 
line  of  fusion  so  that  the  extraembryonic  body  cavity  which  has  been  carried  up 
dorsally  over  the  embryo  in  the  amniotic  folds  becomes  continuous  across  the 
mid-dorsal  line.  A  double  membrane  or  rather  two  membranes  are  thus 
formed  which  extend  over  the  embryo.  The  outer  membrane  is  the  chorion 
and  is  composed  from  without  inward  of  ectoderm  and  parietal  mesoderm. 
The  inner  membrane  is  the  amnion  and  is  composed  from  without  inward  of 
parietal  mesoderm  and  ectoderm  (Fig.  100,  5).  Between  the  amnion  and  the 
chorion  is  a  portion  of  the  extraembryonic  body  cavity,  which,  as  already 
mentioned,  was  carried  dorsally  with  the  amniotic  folds  (Fig.  100,  2,  3,  4  and  5). 

Sclefotome       Myotome 


Entode 


Pronephric 
tubule 


FIG.  101. — Transverse  section  of  a  dog  embryo  with  19  primitive  segments.     Bonnet. 
Section  taken  through  sixth  segment. 


In  the  manner  just  described  the  amnion  becomes  a  sac  which  at  first  en- 
closes the  embryo  laterally,  and  then  laterally  and  dorsally  (Fig.  101).  Later 
as  the  embryo  becomes  constricted  off  from  the  underlying  cavity,  the  amnion 
encloses  it  entirely  except  over  a  small  area  on  the  ventral  side  where  the  embryo 
is  attached  to  the  yolk  sac  (Fig.  100,  3,  4  and  5). 

While  the  amnion  is  being  formed,  the  mesoderm  continues  to  extend 
around  the  vesicle  between  the  ectoderm  and  the  entoderm.  At  the  same  time 
it  splits  into  parietal  and  visceral  layers,  of  which  the  parietal  is  applied  to  the 
ectoderm,  and  the  visceral  to  the  entoderm.  In  this  way  the  extraembryonic 
body  cavity  gradually  extends  farther  and  farther  around  the  vesicle  until 
finally  the  somatopleure  is  completely  separated  from  the  splanchnopleure 
(Fig.  100,  3,  4  and  5).  The  extraembryonic  somatopleure  now  forms  a  com- 
plete wall  for  the  vesicle  and  constitutes  the  chorion.  The  extraembryonic 
splanchnopleure  forms  a  complete  wall  for  the  yolk  cavity  and  constitutes  the 
wall  of  the  yolk  sac.  The  proximal  portion  of  the  yolk  sac  becomes  constricted 


FCETAL  MEMBRANES.  107 

to  form  the  yolk  stalk  which  connects  the  yolk  sac  with  the  ventral  side  of  the 
embryonic  body  (Fig.  100,  5). 

While  the  processes  just  described  have  been  taking  place,  an  evagination  ap- 
pears pushing  out  from  the  ventral  side  of  the  caudal  end  of  the  gut  (Fig.  100, 4). 
This  evagination  grows  out  into  the  extraembryonic  body  cavity  (exo- 
coelom),  pushing  before  it  the  visceral  layer  of  mesoderm,  thus  giving  rise  to  a 
thin-walled  sac  which  communicates  writh  the  gut — the  allantois  (Fig.  100,  5). 
At  this  stage  the  embryonic  body,  with  its  surrounding  amnion  and  appended 
yolk  sac  and  allantois,  lies  within  the  large  vesicle  formed  by  the  chorion.  Up 
to  this  point  the  development  resembles  that  in  the  chick. 

In  succeeding  stages  a  new  connection  is  established  between  the  embryo  and 
the  chorion  in  the  following  manner :  The  amnion  enlarges  and  fills  relatively 
more  of  the  cavity  within  the  chorion,  while  the  yolk  sac  becomes  smaller  and 
the  yolk  stalk  much  attenuated  (Fig.  100,  6).  At  the  same  time  the  allantois 
also  becomes  attenuated  and  its  distal  end  comes  in  contact  with  the  chorion 
(Fig.  100,  6).  The  growth  of  the  amnion  results  in  the  pushing  together  of  the 
attenuated  yolk  stalk  and  allantois  so  that  they  lie  parallel  to  each  other  (Fig. 
100,  6),  and  are  together  invested  by  a  portion  of  the  amnion.  As  already 
described,  both  yolk  stalk  and  allantois  are  composed  of  entoderm  and 
mesoderm  while  the  amnion  is  composed  of  mesoderm  and  ectoderm.  Con- 
sequently when  the  three  structures  come  together  and  fuse,  there  is  formed 
a  mass  of  mesoderm  which  contains  the  entoderm  of  the  yolk  stalk  or  vitelline 
duct  and  the  entoderm  of  the  allantois  or  allantoic  duct,  and  which  is  sur- 
rounded by  the  ectoderm  of  the  amnion.  The  fusion  of  these  three  structures 
in  this  region  thus  produces  a  slender  cord  of  tissue  which  forms  the  union 
between  the  embryo  and  the  chorion  and  which  is  known  as  the  umbilical  cord 
(Fig.  100,  6). 

In  Mammals  the  yolk  sac  contains  little  or  no  yolk  and  consequently  can 
furnish  but  little  nutriment  for  the  embryo;  but  the  union  of  the  allantois  with 
the  chorion,  mentioned  in  the  preceding  paragraph,  allows  the  allantoic  blood 
vessels  to  come  into  connection  with  the  chorion.  And  since  in  Mammals  the 
chorion  is  the  means  of  establishing  the  communication  between  the  embryo 
and  the  mother,  the  allantoic  (umbilical)  vessels  assume  the  function  of  carrying 
nutrient  materials  to  the  embryo  and  also  of  carrying  away  from  the  embryo  its 
waste  products.  (See  p.  223.) 

Further  Development  of  the  Chorion. 

Up  through  the  stages  which  have  been  described  the  correspondence  in  the 
development  of  the  foetal  membranes  in  Reptiles,  Birds  and  Mammals  is  clear. 
From  now  on,  the  course  of  development  in  Mammals  becomes  more  and 
more  divergent.  The  extensive  development  of  the  yolk  and  yolk  sac  with  its 


108 


TEXT-BOOK  OF  EMBRYOLOGY. 


vascular  system  in  the  egg-laying  Amniotes  has  been  noted.  This  is  dependent 
upon  the  fact  that  the  embryo  very  early  in  its  existence  loses  its  nutritional  con- 
nection with  its  mother  and  is  therefore  dependent  for  its  food  upon  the  yolk 
stored  up  within  the  egg.  This  condition  obtains  up  through  the  lowest  order 
of  Mammals,  the  Monotremes,  which  are  egg-laying  animals.  The  Marsupials 
give  birth  to  young  of  very  immature  development.  In  these  two  orders  of 
Mammals  the  foetal  membranes  present  essentially  the  same  condition  as  in 
Birds  and  Reptiles.  The  chorion  in  Marsupials,  however,  lies  in  close  ap- 
position to  the  vascular  uterine  mucosa  and  perhaps  provides  for  the  passage  of 


Chorion 


Muscularis 


FIG.  102. — Vertical  section  through  wall  of  uterus  and  chorion  of  a  pig.     Photograph. 

Note  especially  the  close  apposition  of  the  chorionic  and  uterine  epithelium  (and  compare  with 

Fig.  103);  note  also  the  enlarged  blood  vessels  in  the  uterine  mucosa. 


nutrition  from  the  mother  to  the  embryo.  In  all  higher  Mammals,  however,  no 
eggs  are  laid  and  the  embryo  early  acquires  an  intimate  nutritional  relation  to 
its  mother.  This  relation  is  maintained  until  the  embryo  has  reached  a  com- 
paratively advanced  stage  of  development.  As  would  be  expected  therefore, 
there  take  place,  coincidently  with  the  change  in  nutritional  relation  between 
mother  and  embryo,  and  dependent  upon  this  changed  relation,  the  already 
noted  decrease  in,  or  entire  loss  of,  yolk  and  at  the  same  time  the  development  of 
a  special  organ  of  relation  between  embryo  and  uterus.  This  organ  is  devel- 
oped mainly  from  the  chorion  which  becomes  highly  specialized  as  compared 
with  the  very  simple  chorion  described  in  the  chick. 


FCETAL  MEMBRANES. 


109 


In  some  Mammals  (e.g.,  pig,  horse,  hippopotamus,  camel)  there  develops  a 
more  intimate  relation  between  the  chorion  and  the  uterine  mucosa.  In  the 
pig,  for  example,  the  chorionic  vesicle  becomes  somewhat  spindle-shaped,  and, 
except  at  its  tapering  ends,  its  surface  is  closely  applied  to  the  surface  of  the 
uterine  mucosa.  On  that  portion  of  the  chorion  which  is  in  contact  with  the 
uterine  mucosa  small  elevations  or  projections  develop  and  fit  into  correspond- 
ing depressions  in  the  mucosa.  These  projections  involve  the  epithelial 
layer  (ectoderm)  of  the  chorion  and  the  adjacent  connective  tissue  (mesoderm) 
(Fig.  102) .  Furthermore,  the  chorionic  epithelial  cells  and  the  uterine  epithelial 


Blood  vessel  in 
uterine  mucosa 


FIG.  103. — From  section  through  wall  of  uterus  and  chorion  of  a  pig,  showing  close  relationship 
between  the  epithelium  of  the  uterus  and  that  of  the  chorion.     Photograph. 

cells  acquire  very  intimate  relations  in  that  the  ends  of  the  former  become 
rounded  and  fit  into  depressions  in  the  ends  of  the  latter  (Fig.  103). 

The  allantois  and  allantoic  vessels  in  the  pig  afford  a  good  example  of  the 
transition  from  the  respiratory  and  excretory  functions  which  they  almost  ex- 
clusively possess  in  Reptiles  and  Birds,  to  the  additional  nutritional  function  of 
these  vessels  in  Mammals.  The  allantoic  sac  becomes  large  and  applies  itself 
to  the  inner  surface  of  the  chorion,  so  that  the  blood  vessels  of  the  allantois  also 
grow  into  and  ramify  in  the  mesodermal  layer  of  the  chorion.  This  brings  the 
allantoic  (umbilical)  blood  vessels  containing  the  foetal  blood  closer  to  the  uterine 
vessels  containing  the  maternal  blood.  The  two  sets  of  vessels  never  come  in 
contact,  however,  being  always  separated  by  the  chorionic  and  uterine  epithe- 


110  TEXT-BOOK  OF  EMBRYOLOGY. 

Hum  and  also  by  some  connective  tissue  of  the  chorion  and  of  the  uterine 
mucosa  (Fig.  103).  Food  materials  for  the  embryo  must,  therefore,  pass  through 
the  connective  tissue  and  the  two  epithelial  layers  in  order  to  get  from  the 
maternal  to  the  fcetal  blood;  and  waste  products  from  the  embryo  must  also  pass 
through  the  same  tissues  to  get  from  the  fcetal  to  the  maternal  blood.  When  the 
fcetal  membranes  of  the  pig  are  expelled  at  birth,  the  rudimentary  chorionic 
villi  simply  withdraw  from  their  sockets  in  the  uterine  mucosa  and  the  chorion 
is  cast  off,  leaving  the  uterine  mucosa  intact. 

In  other  Mammals,  the  attachment  of  the  chorion  to  the  mucous  membrane 
of  the  uterus  is  restricted  to  certain  definite,  highly  specialized  areas.  This 
means  that  the  villi  which  at  first  developed  over  the  entire  chorion,  disappear 
from  the  -greater  part  of.  it.  Those  villi  which  remain  are  limited  to  a  definite 
area  or  areas  and  develop  extensive  arborizations. /.  Moreover,  they  do  not 


FIG.  104. — Chorion  of  sheep,  showing  cotyledonary  placenta.     O.  SchuHze. 

simply  fit  into  depressions  in  the  uterine  mucosa,  but  become  much  more 
closely  attached  to  it  while  the  mucosa  increases  in  thickness  and  in  vascularity 
over  the  villous  areas.  There  are  thus  formed  two  distinct  though  intimately 
associated  parts  of  a  structure  which  is  known  as  the  placenta — the  uterine  part 
being  designated  the  maternal  placenta  or  placenta  uterina,  the  fcetal  part  the 
placenta  j&talis.  Such  Mammals  are  grouped  as  Placentalia.  In  the  sheep 
and  cow  a  number  of  placentae — multiple  placentce — are  normally  present  (Fig. 
104).  In  the  dog  and  cat  the  placenta  takes  the  shape  of  a  band  or  a  zone 
of  specialized  tissue  encircling  the  germ  vesicle.  This  is  known  as  a  zonular 
placenta.  In  man  a  single  discoidal  area  develops — discoidal  placenta. 

These  different  forms  of  placentae  vary  also  in  regard  to  the  intimacy  with 
which  maternal  and  fcetal  parts  are  associated.  Thus,  for  example,  in  the 
multiple  placentae  of  the  cow  and  sheep,  the  fcetal  placentae  may  be  easily 


FCETAL  MEMBRANES.  Ill 

pulled  away  from  the  maternal  placentae;  while  in  the  discoidal  placenta  of 
man,  maternal  and  fcetal  parts  are  so  closely  related  that  both  come  away  to- 
gether as  the  after-birth  or  decidua. 

THE  FCETAL  MEMBRANES  IN  MAN. 

The  fcetal  membranes  in  man  are  characterized  by  the  early  development  of 
the  amnion,  the  development  of  an  extremely  complicated  discoidal  placenta  and 
the  rudimentary  condition  of  the  yolk  sac  and'allantois.  The  high  develop- 
ment of  the  placenta — the  organ  of  interchange  between  foetal  and  maternal 
circulation — is  undoubtedly  dependent  upon  the  very  long  period  of  gestation 
during  which  the  human  foetus  leads  an  entirely  parasitic  existence,  being 
dependent  wholly  upon  the  mother  for  nutrition  and  respiration.  The  exten- 
sive development  of  the  placenta  in  turn  explains  the  rudimentary  condition  of 
the  yolk  sac  and  stalk  and  of  the  allantois,  the  nutritional  and  respiratory  func- 
tions of  these  large  and  important  organs  in  some  of  the  lower  animals,  being  hi 
man  taken  up  by  the  placenta. 

The  Amnion. 

In  describing  the  development  of  the  germ  layers  in  the  human  embryo, 
comparisons  were  made  between  one  of  the  youngest  known  human  embryos — • 
that  of  Peters — and  the  embryos  of  the  bat  and  mole  (p.  87).  Reference  to  this 
description  and  to  the  figures  shows  that  in  the  bat  and  mole  the  amnion  is 
formed,  not  as  in  the  chick  and  rabbit  by  dorsal  foldings  of  the  somatopleure 
and  fusion  of  these  folds,  but  in  situ  by  a  breaking  down  of  some  of  the  cells  of 
the  inner  cell  mass  and  consequent  cavity  formation.  In  Peters'  embryo  the 
amnion  is  already  present  as  a  closed  cavity.  The  earlier  stages  in  its  forma- 
tion are  not  known.  As  in  the  case  of  the  germ  layers,  however,  the  appear- 
ances in  sections  are  so  closely  similar  as  to  suggest  at  least,  that  the  human 
amnion  is  formed  in  the  same  manner  as  that  of  the  bat  and  mole. 

In  Peters'  ovum  (Fig.  83),  also  in  Bryce-Teacher's  (Fig.  106),  the 
amniotic  cavity  is  seen  already  formed.  It  is  roofed  by  a  single  layer 
of  flat  cells  apparently  analogous  to  the  trophoderm  of  the  bat  (Fig.  52). 
As  in  the  bat  and  chick  this  layer  is  continuous  with  the  higher  ecto- 
derm of  the  embryo  proper  as  represented  here  by  the  embryonic  disk.  The 
extraembryonic  mesoderm  is  already  present  at  this  stage  between  the  ecto- 
derm of  the  amnion  and  the  trophoderm,  the  epithelial  cells  of  the  latter 
being  seen  on  the  surface.  Ventrally  lies  the  yolk  sac  lined  with  entoderm, 
while  laterally  between  the  entoderm  and  ectoderm  is  seen  the  embryonic 
mesoderm.  This  formation  of  the  amnion  in  situ  considerably  shortens  the 
process  of  amnion  formation  as  compared  with  that  in  most  of  the  lower 
animals,  where  it  is  formed  by  dorsal  foldings.  This  results  in  the  very  early 


112  TEXT-BOOK  OF  EMBRYOLOGY. 

formation  of  a  complete  amnion  and  amniotic  cavity  in  such  forms  as  the  bat, 
mole  and  man. 

The  human  amniotic  cavity  is  at  first  small,  the  amnion  covering  only  the 
dorsum  of  the  embryo  to  which  it  is  closely  applied.  The  dorsal  surface  of  the 
disk  is  at  first  concave,  then  flat,  and  later  its  margins  curve  ventrally  as  the  flat 
disk  becomes  transformed  into  the  definite  shape  of  the  embryonic  body.  As 
the  margins  of  the  disk  bend  ventrally  they  carry  with  them  the  attached  amnion. 
As  the  embryo  becomes  constricted  off  from  the  yolk  sac,  the  amnion  is  attached 
only  ventrally  in  the  region  of  the  developing  umbilical  cord.  With  the 
exception  of  this  attachment  the  embryo  thus  comes  to  lie  free,  floating  in 
the  amniotic  fluid  (Fig.  100,  6). 

The  amniotic  cavity,  at  first  small,  increases  rapidly  in  size  and  by  the  third 
month  has  reached  the  limits  of  the  chorionic  vesicle  completely  filling  it.  It 
then  attaches  itself  loosely  to  the  overlying  chorion  thus  completely  obliterating 
the  extraembryonic  body  cavity.  The  amnion  consists  everywhere  of  two 
layers,  an  outer  ectoderm,  the  cells  of  which  are  at  first  flat,  later  cuboidal  or 
even  columnar,  and  an  inner  layer  of  somatic  mesoderm.  At  the  dermal  navel 
(p.  101)  the  amniotic  ectoderm  is  continuous  with  the  surface  ectoderm  (later 
epidermis)  of  the  embryo.  Some  writers  consider  the  fact  that  the  epithelial 
covering  of  the  umbilical  cord  is  stratified  as  indicating  that  it  is  derived  from 
embryonic  ectoderm  rather  than  from  amniotic  ectoderm,  and  describe  the 
transition  between  the  two  as  taking  place  not  at  the  dermal  umbilicus  but  at 
the  attachment  of  the  cord  to  the  placenta.  As  in  lower  forms  (p.  98)  the 
walls  of  the  amniotic  cavity  contain  contractile  elements  which  determine 
rhythmical  contractions  of  the  amnion. 

The  human  amniotic  fluid  is  a  thin,  watery  fluid  of  slightly  alkaline  reaction 
containing  about  one  per  cent,  of  solids,  chiefly  urea,  albumin  and  grape- 
sugar.  The  origin  of  the  fluid  is  not  known.  By  some  it  is  believed  to  be 
mainly  a  secretion  of  the  maternal  tissues,  by  others  as  largely  of  fcetal  origin. 
The  urea  it  contains  is  probably  excreted  by  the  fcetal  kidneys. 

When  the  amount  of  amniotic  fluid  is  excessive  the  condition  is  known  as 
hydramnios.  If,  as  is  sometimes  the  case,  the  amniotic  fluid  is  present  in  very 
small  amount,  adhesions  may  form  between  the  amnion  and  the  embryo. 
These  may  result  in  malformations.  With  or  without  abnormality  in  the 
amount  of  amniotic  fluid,  bands  of  fibrous  tissue  may  stretch  across  the  cavity. 
If  sufficiently  strong  these  may  produce  such  malformations  as  splitting  of 
a  lip  or  of  the  nose,  or  the  partial  or  complete  amputation  of  a  limb. 

In  labor  a  portion  of  the  amnion  filled  with  fluid  usually  precedes  the  head 
through  the  cervical  canal.  It  is  rounded  or  conical,  and  becoming  distended 
and  tense  with  each  uterine  contraction  or  labor  pain,  serves  as  the  natural 
and  most  efficient  dilator  of  the  cervix.  When  the  cervix  is  partially  or  com- 


FCETAL  MEMBRANES.  113 

pletely  dilated,  the  amnion  usually  ruptures — " rupture  of  the  membranes" — 
and  all  or  a  part  of  the  amniotic  fluid  escapes  as  the  "waters."  Usually  a 
varying  amount  of  the  fluid  remains  behind  the  embryo  being  kept  there  by  the 
head  completely  corking  the  cervix.  This  escapes  with  the  birth  of  the  child. 
In  some  cases  the  amnion  ruptures  at  the  beginning  of  labor,  before  there  has 
been  any  dilatation  of  the  cervix.  The  dilating  must  then  be  done  by  the 
child's  head  or  other  presenting  part.  These  are  much  less  adapted  to  the 
purpose  than  the  bag  of  membranes  and  the  result  is  usually  a  difficult  and 
protracted  "dry  "  labor.  Rarely  the  amnion  fails  to  rupture  during  labor  and 
the  child  is  born  within  the  intact  bag  of  membranes.  Such  a  child  is  said  to 
be  born  with  a  "caul." 

The  Yolk  Sac. 

In  the  human  embryo  the  yolk  sac  is  but  a  rudiment  of  the  large  and  im- 
portant organ  found  in  some  of  the  lower  animals.  It  develops  early  and  at  the 
end  of  the  second  week  is  an  almost  spherical  sac  with  a  wide  opening  into  the 
intestine  (Fig.  121),  there  being  but  a  slight  constriction  between  the  embryo 
and  the  yolk  sac.  During  the  third  week  the  yolk  sac  becomes  decidedly  con- 
stricted off  from  the  embryo,  remaining  connected,  however,  with  the  intestine 
by  means  of  a  long  pedicle,  the  yolk  stalk  or  vitelline  duct  (Fig.  123).  As  the 
placenta  is  formed,  and  at  the  same  time  the  umbilical  cord,  the  yolk  sac  becomes 
incorporated  with  the  former,  where  it  may  sometimes  be  found  by  careful 
search  after  birth,  wrhile  the  yolk  stalk  becomes  reduced  to  a  strand  of  cells 
which  traverses  the  entire  length  of  the  umbilical  cord  (p.  130). 

Whatever  function  the  rudimentary  human  yolk  sac  has,  must  be  performed 
early,  as  both  sac  and  stalk  soon  undergo  regressive  changes.  Although  no  true 
yolk  is  present,  the  sac  at  first  contains  fluid  and  its  thick  outer  mesodermal  layer 
is  the  place  of  earliest  blood  and  blood  vessel  formation.  This  would  seem  to 
indicate  that  like  the  larger  yolk  sac  of  lower  animals,  the  human  yolk  sac 
serves  temporarily  as  a  blood-forming  organ. 

In  about  three  per  cent,  of  cases  that  portion  of  the  yolk  stalk  which  lies 
between  the  intestine  and  the  umbilicus  fails  to  degenerate,  retaining  its  lumen 
and  its  connection  with  the  intestine.  It  is  then  known  as  MeckeVs  diverticulum 
and  is  of  considerable  surgical  importance,  as  it  may  become  invaginated  into 
the  small  intestine  and  thus  cause  obstruction  of  the  bowel.  The  blind  end  of 
the  diverticulum  may  remain  attached  to  the  umbilicus,  or  it  may  become  free, 
or  in  rare  cases  the  stalk  may  retain  a  lumen  from  the  intestine  to  the  umbilicus, 
through  which  faeces  may  escape — "faecal  fistula."  Occasionally  a  portion  of 
the  gut  from  which  the  yolk  stalk  is  given  off  extends  for  a  short  distance  into 
the  cord.  If,  as  is  sometimes  the  case,  this  extension  fails  to  retract  before 
birth,  a  congenital  umbilical  hernia  is  the  result  (see  Chap.  XIX). 


114  TEXT-BOOK  OF  EMBRYOLOGY. 

The  Allantois. 

The  human  allantois,  while  analogous  to  the  allantois  of  Birds  and  Reptiles, 
shows  certain  marked  peculiarities  in  its  development,  in  its  relation  to  sur- 
rounding structures  and  in  its  functions. 

Its  development  is  peculiar  in  that  it  does  not  push  out,  as,  for  example,  in 
the  chick,  as  an  evagination  from  the  primitive  gut  into  the  extraembryonic 
body  cavity,  for  at  the  very  early  stage  at  which  the  human  allantois  first  ap- 
pears, the  primitive  gut  is  not  as  yet  constricted  off  from  the  yolk  sac  and  there 
is  no  extraembryonic  body  cavity  into  which  the  allantois  can  extend.  It  will  be 
remembered  that  in  the  formation  of  the  germ  layers  and  in  the  development  of 
the  amnion  the  human  embryo  shows  a  marked  tendency,  as  compared  with 
lower  forms,  toward  a  shortening  of  the  developmental  process.  This  ab- 
breviation and  consequent  very  early  formation  applies  also  to  the  allantois.  As 
the  embryonic  body  assumes  definite  shape  and  the  amnion  is  formed,  there  is 
not  the  complete  separation  of  amnion  from  the  chorion  seen,  for  example,  in  the 
chick,  the  embryo  remaining  connected  posteriorly  with  the  chorion  by  means  of 
a  short  thick  cord  of  mesodermic  tissue.  This  is  known  as  the  belly  stalk.  Into 
this  solid  cord  of  mesodermic  tissue  which  connects  the  embryo  with  the 
chorion,  entodermic  cells  extend.  These  are  derived  from  the  embryonic  en- 
toderm  before  the  constriction  which  differentiates  the  primitive  gut  from  the 
yolk  sac  has  made  its  appearance  (Fig.  85).  According  to  some  there  is  a  true 
evagination  from  the  entodermic  sac  quite  analogous  to  the  evagination  in  the 
chick,  resulting  in  a  long  slender  tube  lined  by  entoderm  and  extending  from 
the  embryo  to  the  chorion.  Others  describe  the  entodermic  outgrowth  as  a 
solid  cord  of  cells.  The  mesodermic  layer  of  the  allantois  is  furnished  by  the 
mesoderm  of  the  belly  stalk.  It  is  to  be  noted  in  this  connection  that  the 
mesoderm  of  the  belly  stalk  is  embryonic  mesoderm  and  that  in  Birds,  for 
example,  this  portion  of  the  mesoderm  splits  into  two  layers,  somatic  and 
splanchnic,  with  the  extraembryonic  body  cavity  between  them.  Into  this 
extraembryonic  body  cavity  the  allantois  extends.  In  man  no  such  splitting 
occurs,  so  that  there  is  no  extraembryonic  body  cavity  into  which  the  allantois 
can  extend.  Instead,  it  grows  out  into  the  belly  stalk. 

The  functions  of  the  human  allantois  are  somewhat  different  from  those  of 
the  allantois  of  the  chick.  In  the  latter  it  is  a  direct  respiratory  organ  in  that  it 
brings  the  embryo  into  relation  with  the  outside  air.  In  man  the  allantois, 
accompanied  by  the  allantoic  (umbilical)  blood  vessels,  comes  into  relation 
with  the  placenta.  As  the  placenta  serves  as  the  medium  of  exchange  between 
fcetal  and  maternal  circulations,  it  acts  as  a  modified  organ  of  respiration.  In 
the  chick  the  allantoic  cavity  also  serves  for  the  reception  of  the  excretions  from 
the  embryo,  the  allantoic  fluid  containing  nitrogenous  excretives.  In  man  all 


FCETAL  MEMBRANES.  115 

such  elimination  is  carried  on  through  the  placenta  and  there  is  consequently 
no  need  for  the  development  of  a  large  allantoic  sac. 

With  development  of  the  placenta,  that  part  of  the  allantoic  stalk  which  lies 
in  the  umbilical  cord  atrophies.  Of  the  embryonic  portion  of  the  allantois, 
or  the  urachus,  on  the  other  hand,  the  proximal  end  communicates  with  the 
urinary  bladder,  while  the  remainder,  which  extends  from  the  bladder  to  the 
umbilicus  becomes  transformed  into  a  fibrous  cord, — the  middle  umbilical 
ligament  (page  401).  Rarely  that  portion  of  the  allantoic  stalk  between  the 
bladder  and  the  umbilicus  remains  patent  and  opening  upon  the  surface 
forms  a  "urinary  fistula,"  allowing  urine  to  escape. 

In  Reptiles  and  Birds  the  omphalomesenteric  vessels,  passing  along  the  yolk 
stalk  and  ramifying  in  the  mesodermal  layer  of  the  yolk  sac,  convey  the  nutrient 
materials  of  the  yolk  to  the  growing  embryo.  Since  the  allantois  is  an  organ  of 
respiration  and  excretion,  the  allantoic  or  umbilical  vessels  have  nothing  to  do 
with  the  actual  nourishment  of  the  embryo  (p.  222).  In  Mammals  the  yolk  sac 
is  of  less  functional  value.  Consequently  the  vitelline  vessels,  although  present 
(Fig.  215),  play  a  less  important  role  in  conveying  nutriment.  The  allantoic 
(umbilical)  vessels,  instead  of  ramifying  in  the  wall  of  the  allantois,  as  in  the 
lower  forms,  come  into  connection  with  the  chorion,  passing  primarily  through 
the  belly  stalk.  Since  the  chorion  becomes  the  organ  of  interchange  between 
the  embryo  and  the  mother,  the  allantoic  vessels  assume  a  new  function,  the 
allantoic  (umbilical)  vein  carrying  food  material  from  the  mother  to  the  em- 
bryo, the  arteries  carrying  waste  products  from  the  embryo  to  the  mother. 
Thus  in  Mammals,  as  the  yolk  sac  and  vitelline  vessels  come  to  play  a  less  im- 
portant role  in  the  nutrition  of  the  embryo,  the  allantoic  vessels,  in  connection 
with  the  chorion,  become  practically  the  only  means  by  which  the  embryo 
receives  its  food-supply. 

The  Chorion  and  the  Decidua. 

When  the  fertilized  ovum  reaches  the  uterus  it  becomes  fixed  or  embedded 
in  the  uterine  mucosa.  Fixation  usually  occurs  in  the  upper  half  of  the  uterus 
but  may  occur  near  the  cervix.  Rarely  the  ovum  becomes  fixed  to  the  mucous 
membrane  of  the  tube  instead  of  to  that  of  the  uterus,  and,  developing  there, 
gives  rise  to  a  "tubal"  pregnancy — one  of  the  forms  of  extrauterine  gestation. 

Until  recently,  it  was  believed  that  the  ovum  became  attached  to  the  surface 
of  the  mucous  membrane.  Recent  studies  upon  some  of  the  youngest  human 
ova  and  upon  those  of  some  of  the  lower  Mammals,  however,  seem  to  indicate 
that  the  ovum  in  some  wray  pushes  itself  into — buries  itself — in  the  uterine 
mucosa  (Fig.  105).  It  is  argued  that  if  the  ovum  simply  attaches  itself  to  the 
surface  of  the  mucosa,  one  would  expect  to  find,  for  a  time  at  least,  epithelium 
between  the  attached  surface  and  the  stroma.  In  a  very  young  human  ovum 


116 


TEXT-BOOK  OF  EMBRYOLOGY. 


no  such  epithelium  was  found  and  the  ovum  had  the  appearance  of  having 
penetrated  the  stroma  by  which  it  was  surrounded  (Fig.  106).  Thus,  for  the 
first  two  weeks  of  gestation,  the  ovum  lies  embedded  in  the  stroma  of  the  uterine 
mucosa,  giving  so  little  surface  indication  of  its  presence  that  it  is  practically 
impossible  to  locate  it  except  by  serial  sections  of  the  entire  mucosa.  After 
two  weeks  the  position  of  the  ovum  begins  to  be  indicated  by  a  slight  prominence 
of  the  mucous  membrane,  the  summit  of  the  prominence  being  marked  by  an 
entrance  plug  consisting  of  coagulum,  cast  off  cells  and  fibrin  (Fig.  83).  In 


Uterine 
epithelium 


Thickening  of 
trophoderm 


Uterine 
epithelium 


Thickening  of  L 

trophoderm 

Degenerating 

uterine  epithelium 


FIG.  105. — Successive  stages  in  the  implantation  of  the  ovum  of  Spermophilus  citillus.     Rejsek. 

a.  Ovum  (blastodermic  vesicle)   lying  free  in  the   uterine  cavity,      b,  Later  stage  in  which  the 

syncytial  knob  (thickening  of  trophoderm)   has  penetrated  the  uterine  epithelium  as  far  as 

the  basement  membrane,     c,  Still  later  stage  in  which  the  trophoderm  has  penetrated  the 

uterine  stroma;  the  cells  of  the  uterine  epithelium  at  the  point  of  entrance  are  degenerating. 

the  Bryce-Teacher  ovum  no  such  entrance  plug  was  found  (Fig.  106).  At 
this  stage  the  plug  contains  no  glands  or  blood  vessels.  Later  it  becomes 
organized  and  replaced  by  connective  tissue.  Whatever  the  mode  of  fixation 
of  the  ovum  to  the  uterus,  there  immediately  result  important  changes  in  the 
uterine  mucosa  which  lead  to  the  formation  of  the  decidua.  These  changes  are 
both  destructive  and  constructive.  They  are  destructive  in  that  the  epithelial 
covering  of  the  ovum,  the  trophoderm,  has  some  solvent  action  on  the  uterine 
mucosa  and  breaks  down  the  walls  of  the  maternal  blood  vessels  thus  allowing 
the  blood  to  flow  around  the  ovum  (Fig.  106).  They  are  constructive  in  that 
they  result  in  the  formation  of  the  decidua. 


FCETAL  MEMBRANES. 


117 


From  their  relation  to  the  ovum  and  to  the  uterus,  the  deciduae  (by  which  is 
meant  the  uterine  mucosa  of  pregnancy)  have  been  divided  into  the  decidua 
farietalis  or  decidua  vera  the  decidua  basalis  or  serotina,  and  the  decidua  cap- 
sularis  or  reflexa. 


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O 

S 


Capillary;   cy*.,  cellular  layer  (cyto-trophoderm) ;  e/>.,  uterine  epithelium;  gl.,  uterine  gland; 
11.  z.,  necrotic  zone  of  decidua  (uterine  mucosa);  P.e.,  point  of  entrance  of  the  ovum;  tro., 


svncvtmm 


(plasmodium,    plasmodi-trophoderm);    tro.1,  masses   of   vacuolating   syncytium 
invading  capillaries.     The  cavity  of  the  blastodermic  vesicle  is  completely  filled  by  mesoderm, 


and  embedded  therein  are  the  amniotic  and  entodermic  (yolk)  vesicles, 
portions  of  the  several  parts  have  been  observed. 


The  natural  pro- 


The  decidua  parietalis  is  the  changed  mucosa  of  the  entire  uterus  with  the 
exception  of  that  portion  to  which  the  ovum  is  attached.  The  decidua  basalis 
is  that  portion  of  the  mucosa  to  which  the  ovum  is  attached  and  which  later 
becomes  the  maternal  part  of  the  placenta.  The  decidua  reflexa  is  either  the 


118 


TEXT-BOOK  OF  EMBRYOLOGY. 


extension  of  the  mucosa  over  the  ovum  or  that  part  of  the  mucosa  under  which 
the  ovum  buries  itself  (Fig.  107). 

It  will  be  remembered  that  surrounding  the  entire  young  ovum  is  the  chorion 
and  that  this  membrane  consists  of  two  layers,  an  outer  ectoderm  (trophoderm) 
and  an  inner  mesoderm.  In  the  youngest  known  human  embryo  the  chorion  is 


Decidua  parietalis 
Decidua  capsularis 

Decidua  basalis       ] 
Chorion  frondosum  I 


Placenta 


FIG.  107. — Semidiagramatic  sagittal  section  of  human  uterus  containing  an 

embryo  of  about  five  weeks.     Allen  Thompson. 

a,  Ventral  (anterior)  surface;  c,  cervix  uteri;  ch,  chorian;  g,  outer  limit  of  decidua; 
m,  muscularis;  p,  dorsal  (posterior)  surface. 


a  shaggy  membrane,  its  entire  surface  being  covered  with  small  projections  or 
villi.  Later  these  villi  disappear  from  all  of  the  chorion  except  that  part  of  it 
which  becomes  attached  to  the  uterine  mucosa  and  forms  the  foetal  part  of  the 
placenta.  The  latter  is  known  as  the  chorion  frondosum,  while  the  smooth 
remainder  of  the  chorion  is  known  as  the  chorion  lave. 
There  are  thus  to  be  considered: 


1.  The  decidua  parietalis. 

2.  The  decidua  capsularis. 

3.  The  decidua  basalis 

4.  The  chorion  frondosum 


forming  the  placenta. 


FCETAL  MEMBRANES.  119 

The  Decidua  Parietalis. — The  changes  in  the  uterine  mucosa  which 
result  in  the  formation  of  the  decidua  parietalis  are  similar  to,  though  more 
extensive  than,  the  changes  which  take  place  during  the  earlier  stages  of  men- 
struation. There  is  congestion  of  the  stroma  with  proliferation  of  the  con- 
nective tissue  elements  and  increase  in  the  length,  breadth  and  tortuosity  of  the 
glands.  These  changes  result  as  in  menstruation  in  thickening  of  the  mucosa 
so  that  at  the  height  of  its  development  the  decidua  parietalis  has  a  thickness  of 
about  i  cm.  It  extends  to  the  internal  os  where  it  ends  abruptly,  there  being  no 
decidua  formed  in  the  cervix. 

In  the  superficial  part  of  the  mucosa  the  glands  wholly  or  almost  wholly 
disappear  and  their  place  is  taken  by  the  proliferating  connective  tissue  of  the 
stroma.  The  result  is  a  layer  of  comparatively  dense  connective  tissue — the 
compact  layer.  Beneath  this  layer  are  found  remains  of  the  uterine  glands  in 
the  shape  of  widely  open,  somewhat  tortuous  spaces  which  extend  for  the  most 
part  parallel  to  the  muscularis.  Some  of  these  glandular  remains  retain  part 
of  their  epithelium.  Lying  in  the  proliferating  stroma,  these  spaces  give  to  this 
layer  the  structure  which  has  led  to  its  being  designated  the  spongy  layer. 

During  the  latter  half  of  pregnancy  the  decidua  parietalis  becomes  greatly 
thinned,  due  apparently  to  pressure  from  the  growing  embryo  with  its  mem- 
branes. With  this  thinning,  the  few  remaining  glands  of  the  compact  layer 
disappear.  The  character  of  the  spongy  layer  changes,  the  glands  collapsing  or 
being  reduced  to  elongated,  narrow  spaces  parallel  to  the  muscularis.  The 
entire  tissue  also  becomes  much  less  vascular  than  in  early  pregnancy. 

If  the  fcetal  membranes  are  in  situ  the  compact  layer  is  in  contact  with  the 
ectodermic  (epithelial)  layer  of  the  chorion.  Next  to  this  lies  the  mesodermic 
(connective  tissue)  layer  of  the  chorion.  Delicate  adhesions  connect  the 
mesodermic  tissue  of  the  chorion  with  the  mesodermic  layer  of  the  amnion. 
Covering  the  latter  is  the  amniotic  ectoderm  (epithelium). 

The  Decidua  Capsularis. — Early  in  its  development  this  has  essentially 
the  same  structure  as  the  decidua  parietalis.  Its  older  or  more  common  name, 
decidua  reflexa,  indicates  the  earlier  idea  that  this  portion  of  the  decidua  repre- 
sents a  growing  around  or  reflection  of  the  uterine  mucosa  upon  the  attached 
ovum.  Peters,  after  examining  the  very  early  ovum  which  bears  his  name, 
came  to  the  apparently  warranted  conclusion  that  instead  of  the  uterine  mucosa 
growing  out  around  the  ovum,  the  ovum  buries  itself  in  the  mucosa,  and  that  by 
the  time  the  ovum  had  reached  the  size  of  the  one  he  examined  (i  mm.),  it  was 
almost  entirely  covered  over  by  the  mucosa  (Fig.  83).  See  also  Fig.  106.  In 
Peters'  ovum  a  coagulum  consisting  of  blood  cells,  other  cast  off  cells  and 
fibrin  marked  the  point  at  which  the  ovum  probably  entered  the  stroma. 
Later  this  is  replaced  by  connective  tissue  and  for  a  considerable  time  the  point 
is  marked  by  an  area  of  scar  tissue. 


120  TEXT-BOOK  OF  EMBRYOLOGY. 

By  about  the  fifth  month  the  rapidly  growing  embryo  with  its  membranes 
has  filled  the  uterine  cavity,  and  the  decidua  capsularis,  now  a  very  thin  trans- 
parent membrane,  is  everywhere  pressed  against  the  decidua  parietalis.  It 
ultimately  either  disappears  (Minot)  or  blends  with  the  decidua  parietalis 
(Leopold,  Bonnet). 

The  Decidua  Basalis. — As  the  decidua  basalis  is  that  part  of  the  mucosa 
to  which  the  chorion  frondosum  is  attached,  it  is  convenient  to  consider  the 
two  structures  together. 

Decidua 


"Fastening"  villi 


Terminal  villi 


Vein 
Chorion 

FIG.  108. — Isolated  villi  from  chorion  frondosum  of  a  human  embryo  of 
eight  weeks.     Kollmann's  Atlas. 

At  a  very  early  stage,  villi  develop  over  the  entire  surface  of  the  chorion 
(Fig.  106).  Very  soon,  however,  the  villi  begin  to  increase  in  number  and  in 
size  over  the  region  of  the  attachment  of  the  ovum  and  to  disappear  from  the 
remainder  of  the  chorion,  thus  leading  to  the  already  mentioned  distinction 
between  the  chorion  frondosum  and  the  chorion  laeve  (p.  118). 

THE  CHORION  FRONDOSUM  or  fcetal  portion  of  the  placenta  consists  of  two 
layers  which  are  not,  however,  sharply  separated. 

1.  The  compact  layer.     This  lies  next  to  the  amnion  and  consists  of  con- 
nective tissue.     At  first  the  latter  is  of  the  more  cellular  embryonal  type.     Later 
it  resembles  adult  fibrous  tissue. 

2.  The  villous  layer.     The  chorionic  villi,  when  they  first  appear,  are  short 


FCETAL  MEMBRANES. 


121 


simple  projections  from  the  epithelial  layer  of  the  chorion  and  consist  wholly  of 
epithelium.  Very  soon,  however,  two  changes  take  place  in  these  projec- 
tions. They  branch  dichotomously  giving  rise  to  secondary  and  tertiary  villi, 
forming  tree-like  structures  (Fig.  108).  At  the  same  time  mesoderm  grows 
into  each  villus  so  that  the  central  part  of  the  originally  solid  epithelial  villus  is 
replaced  by  connective  tissue,  which  thus  forms  a  core  or  axis.  This  connective 
tissue  core  is  at  first  free  from  blood  vessels,  but  toward  the  end  of  the  third  week 
terminals  of  the  umbilical  (allantoic)  vessels  grow  out  into  the  connective  tissue 
and  the  villus  becomes  vascular.  Each  villus  now  consists  of  a  core  of  vascular 
mesodermic  tissue  (embryonal  connective  tissue)  covered  over  by  trophoderm 


Syncytium 


Cellular  layer 
(of  Langhans) 


Blood  vessels 


Mesoderm 
(core  of  villus) 


Intervillous 
space 


FIG.  109. — Section  of  proximal  end  of  villus  from  chorion  frondosum  of  human  embryo 

of  two  months.     Photograph. 

In  the  space  above  the  villus  is  a  mass  of  cells  such  as  are  invariably  found  among  or  attached  to 

the  villi  (see  text,  page  126). 


(epithelium).  At  first  the  epithelium  of  the  villus  consists  of  distinctly  outlined 
cells.  Very  soon,  however,  the  epithelium  shows  a  differentiation  into  two 
layers.  The  inner  layer  lying  next  to  the  mesoderm  is  called  the  layer  of 
Langhans  or  cyto-trophoderm.  Its  cell  boundaries  are  distinct  and  its  nuclei 
frequently  show  mitosis.  The  outer  covering  layer  consists  of  cells  the  bodies 
of  which  have  fused  to  form  a  syncytium — the  syncytial  layer  or  plasmodi- 
trophoderm.  This  is  a  layer  of  densely  stained  protoplasm  of  uneven  thickness 
(Figs.  109  and  no).  It  contains  small  nuclei  which  take  a  dark  stain.  As 
this  layer  is  constantly  growing,  and  as  these  nuclei  do  not  show  mitosis,  it  has 
been  suggested  that  they  probably  multiply  by  direct  division. 


122  TEXT-BOOK  OF  EMBRYOLOGY. 

At  an  early  stage  large  masses  of  cells  appear  among  the  villi,  sometimes  being 
attached  to  the  villi  (Figs.  109  and  in).  The  origin  of  these  masses  is  not  known 
with  certainty.  They  may  represent  thickenings  of  the  syncytium  in  which  the 
cell  boundaries  have  reappeared,  or  they  may  represent  outgrowths  from 
Langhans'  layer.  In  some  cases  the  cells  are  small  with  darkly  staining  nuclei, 
in  other  cases  large  and  homogeneous  with  large  vesicular  nuclei.  Large 
multinuclear  cells,  or  giant  cells,  with  homogeneous  cytoplasm,  also  appear. 
In  some  cases  they  apparently  lie  free  in  the  intervillous  spaces  although 


Hofbauer's  cell 


Capillary 


FIG.  no. — Transverse  section  of  chorion  villus  from  human  embryo  of  two  months,  showing  meso- 
dermal  core  of  villus  and  surrounding  cellular  layer  (cyto-trophoderm)  and  syncytium  (plas- 
modi-trophoderm).  Hofbauer's  cell  is  an  example  of  large  cells  found  in  the  villi,  but  the 
significance  of  which  is  not  known.  From  retouched  photograph.  Grosser. 


it  is  claimed  by  some  investigators  that  they  merely  represent  sections  of 
tips  of  the  syncytial  masses.  A  structure  known  as  canalized  fibrin  (which 
takes  a  brilliant  eosin  stain)  begins  to  develop  in  the  earlier  months  of  preg- 
nancy and  gradually  increases  in  amount  during  the  later  stages.  It  is  found 
in  relation  with  the  large  cell  masses  among  the  villi  and  is  probably  a  degen- 
eration product  of  these  masses. 

In  the  later  months  of  pregnancy  the  covering  layer  of  the  villi  loses  its 
distinctly  epithelial  character,  the  cyto-trophoderm  or  cellular  layer  disappearing 
and  the  plasmodi-trophoderm  or  syncytial  layer  becoming  reduced  to  a  thin 


FCETAL  MEMBRANES. 


123 


homogeneous  membrane.  At  points  in  this  membrane  are  knob-like  projections 
composed  of  darkly  staining  nuclei.  These  are  known  as  nuclear  groups,  or 
proliferation  islands,  and  probably  represent  the  proximal  portions  of  the  large 
cell  masses  already  described  (compare  Figs,  no  and  112). 

Certain  of  the  uterine  stroma  cells  increase  greatly  in  size  and  become  the 
deddual  cells.  These  are  large  cells — 30  to  100  microns — and  vary  in  shape. 
Late  in  pregnancy  they  acquire  a  brownish  color  and  give  this  color  to  the 
superficial  layer  of  the  decidua  parietalis.  Each  cell  usually  contains  a  single 


"Giant"  cell 
Syncytium 


Canalized 
fibrin 


Syncytium 


Trophoderm 
mass 


FIG.  in. — Section  of  chorion  of  human  embryo  of  one  month  (9  mm.).     Grosser. 


large  nucleus.  Some  contain  two  or  three  nuclei.  A  few  are  frequently 
multinuclear. 

Some  of  the  chorionic  villi  float  freely  in  the  blood  spaces  of  the  maternal 
placenta — floating  'uilli;  others  are  attached  to  the  maternal  tissue — fastening 
villi.  The  villi  are  separated  into  larger  and  smaller  groups  or  lobules  by  the 
growth  of  connective  tissue  septa  from  the  maternal  placenta  down  into  the 
decidua  basalis.  These  are  known  as  placental  septa,  while  the  groups  of 
chorionic  villi  are  known  as  cotyledons  (Figs.  113  and  115). 

Both  decidual  cells  and  chorionic  villi  are  important  from  a  diagnostic 


124 


TEXT-BOOK  OF  EMBRYOLOGY. 


standpoint,  as  the  finding  of  them  in  curettings  or  in  a  uterine  discharge  may 
be  accepted  as  proof  of  pregnancy. 

During  the  early  months  of  pregnancy — first  four  months — the  decidua 
basalis  has  essentially  the  same  structure  as  the  decidua  parietalis.  Its  surface 
epithelium  disappears  very  early,  perhaps  even  before  the  attachment  of  the 
ovum.  The  glandular  elements  and  the  connective  tissue  undergo  the  same 
changes  as  in  the  decidua  parietalis  and  here  also  result  in  the  differentiation 
of  a  compact  layer  and  a  spongy  layer.  Both  layers  are  much  thinner  than 
in  the  decidua  parietalis. 

As  already  noted,  connective  tissue  septa  pass  from  the  superficial  layer  of  the 
decidua  basalis  down  into  the  fcetal  placenta  subdividing  the  latter  into  cotyle- 
dons. At  the  margin  of  the  placenta  the  decidua  basalis  passes  over  into  the 


Remnant  of  syncytium 
Capillaries 


Remnant 
of  syncytium 


y* Capillary 

JSfcS^ai 
Nuclear  group 

FIG.  112. — Transverse  sections  of  chorionic  villi  at  the  end  of  pregnancy.     Schaper. 

thicker  decidua  parietalis  and  here  the  chorion  is  firmly  attached  to  the  decidua 
basalis. 

There  still  remains  to  be  considered  what  may  be  called  the  border  zone 
between  the  decidua  basalis  and  the  chorion  frondosum.  The  whole  purpose 
of  the  placenta  is  the  interchange  of  materials  between  the  maternal  and  fcetal 
circulation.  It  is  in  the  border  zone  that  this  interchange  takes  place.  The 
entire  structure  of  this  zone  is  for  this  function,  while  all  the  rest  of  the  placenta 
serves  to  transport  the  blood  to  and  from  this  area.  We  have  considered  on  the 
maternal  side  the  structure  of  the  superficial  (compact)  layer  of  the  decidua 
basalis  (p.  119),  on  the  fcetal  side  the  structures  of  the  villous  layer  of  the  chorion 
frondosum  (p.  120).  Unfortunately,  this  border  zone  has  an  extremely  com- 
plicated structure  which  is  difficult  of  interpretation  in  the  usual  microscopic 
section.  This  has  led  to  much  confusion  in  description  and  many  differences 
of  opinion  as  to  actual  structure.  We  can  here  consider  only  the  more  generally 


FCETAL  MEMBRANES. 


125 


accepted  facts,  referring  the  student  to  special  articles  on  the  subject  for  further 
details. 

In  the  fully  developed  placenta,  the  chorionic  villi  lie  either  free  (floating 


villi)  or  attached  to  the  decidua  (fastening  villi)  in  what  are  known  as  inter- 
villous  spaces  (Fig.  113).     In  sections  the  villi  are,  on  account  of  their  structure, 


126 


TEXT-BOOK  OF  EMBRYOLOGY. 


Blood  vessel 


Base  of  villus 


in  section 


^:-lv;USi-ii^I:^      \ Uterine  glards 
^=j^^_.'?!??Ir!r'    j  Base  of  decidua 


,Muscular  coat 
of  uterus 


FlG.  114. — Vertical  section  through  wall  of  uterus  and  placenta  in  situ;  about  seven  months' 

development.     Minot. 


FCETAL  MEMBRANES. 


127 


cut  in  all  directions,  many  sections  of  villi  being  entirely  free  from  their  basal 
connections.  The  villi  thus  present  the  appearance  of  projections,  peninsulas, 
or  islands  lying  in  spaces  filled  with  blood  (Fig.  114). 

Branches  from  the  arteries  of  the  uterine  muscularis  enter  the  decidua  basa- 
lis.  They  take  very  tortuous  courses  through  the  latter  and  in  it  lose  their  con- 
nective tissue  and  muscular  coats,  and,  while  of  considerably  larger  diameter 
than  most  capillaries,  become  reduced  to  endothelial  tubes.  These  follow  the 
intervillous  (placental)  septa  in  which  they  branch  and  from  which  they  finally 
open  directly  into  the  intervillous  spaces  along  the  edges  of  the  cotyledons. 
The  maternal  blood  is  thus  poured  into  the  intervillous  spaces  at  their  peri- 
phery. After  flowing  through  them  it  passes  into  veins  which  leave  the 
intervillous  spaces  near  the  center  of  the  cotyledons  (Fig.  113). 


Chorion  laeve  +.. 
Decidua  parietalis' 


r"  Decidua  basalis 


Cotyledon 
(lob'e) 


Cotyledon 
(lobe) 


FIG.  115. — Placenta  at  birth,  seen  from  the  uterine  side.     Bonnet. 

The  relation  of  these  spaces  to  the  maternal  blood  vessels  is  not  easy  to  make 
out  in  ordinary  sections,  but  many  observations  have  established  the  fact  that 
both  arteries  and  veins  open  directly  into  the  spaces.  The  entire  system  of 
intervillous  spaces  may  thus  be  considered  as  a  part  of,  or  an  appendage  to,  the 
maternal  vascular  system,  the  maternal  blood  flowing  from  the  arteries  into 
these  spaces  and  returning  from  these  spaces  to  the  mother  through  the  veins. 
The  fcetal  blood,  on  the  other  hand,  circulates  in  the  capillaries  of  the  connective 
tissue  of  the  villi  separated  from  the  maternal  blood  of  the  intervillous  spaces  by 
the  epithelial  villous  covering  already  described  (p.  121).  It  is  between  the 
maternal  blood  of  the  intervillous  spaces  and  the  foetal  blood  in  the  villous 
capillaries  that  the  interchange  of  material  takes  place.  Both  the  maternal 
and  fcetal  vascular  systems  are  clcsed  systems  so  that  no  blood  can  pass  directly 


128  TEXT-BOOK  OF  EMBRYOLOGY. 

from  mother  to  foetus  or  from  foetus  to  mother.  This  can  be  absolutely  proved  in 
early  pregnancy  by  the  fact  that  nucleated  red  cells  are  at  this  stage  constantly 
present  in  the  blood  of  the  foetus  but  never  normally  present  in  the  maternal 
circulation.  The  normal  circulation  of  blood  through  spaces  unlined  by  endo- 
thelium  is  such  a  remarkable  exception  in  histology  that  repeated  attempts 
have  been  made  to  demonstrate  an  endothelial  lining  to  the  intervillous  spaces 
but,  up  to  the  present  time,  no  such  lining  has  been  found. 

The  manner  in  which  the  intervillous  spaces  are  formed  still  remains  the 
subject  of  much  controversy.  The  similarity  of  development  in  the  human 
ovum  and  in  the  ovum  of  the  bat  has  already  been  noted.  In  the  bat  the 
chorion  when  first  formed  consists  of  two  thin  layers,  an  inner  mesodermal 
layer  and  an  outer  ectodermal  layer  (trophoderm).  From  analogy  there  is 
every  reason  to  believe  that  the  early  human  chorion  has  the  same  struc- 
ture. Proof  of  this  is,  however,  as  yet  wanting,  as  in  the  earliest  human  ova 
the  trophoderm  is  already  a  thick  layer.  There  are  also  present  over  the 
entire  surface  of  the  chorion  and  thus  in  contact  not  only  with  the  future 
decidua  basalis  but  also  in  contact  with  the  entire  future  decidua  capsularis, 
well  developed  villi,  each  consisting  of  a  core  of  mesoderm  and  of  a  thick  covering 
of  trophoderm  (Fig.  83).  Between  the  villi,  bounded  by  the  villi  and  by  the 
decidua,  are  pools  of  maternal  blood.  Peters  suggested  that  rapid  prolifera- 
tion of  the  cells  of  the  trophoderm  might  result  in  an  opening  up  of  the  maternal 
vessels  with  which  they  came  in  contact  and  give  rise  to  repeated  effusions  of 
maternal  blood.  This  blood  would  be  poured  out  mainly  within  the  tropho- 
derm but  bounded  externally  by  the  decidua.  The  blood  pools  thus  formed 
would  represent  the  first  stage  in  the  formation  of  the  intervillous  spaces.  Ac- 
cording to  Bonnet  and  others  the  chorionic  villi  of  the  developing  placenta  are 
constantly  opening  up  new  decidual  vessels,  the  trophoderm  eroding  or  dis- 
solving more  and  more  decidual  tissue,  so  that  the  intervillous  spaces  are  con- 
stantly increasing  in  size  with  growth  of  the  placenta. 

The  placenta  at  birth  is  a  discoid  mass  of  tissue  between  15  and  20  cm.  in 
diameter,  about  3  to  4  cm.  thick  and  weighs  from  500  to  1200  grms.  As  its 
area  of  attachment  marks  the  point  where  the  ovum  becomes  fixed  to  the 
uterine  mucosa  and  as  the  point  of  fixation  of  the  ovum  varies,  the  placenta  may 
be  attached  to  any  portion  of  the  uterine  wall.  It  is  most  frequently  attached 
in  the  region  of  the  fundus  and  more  frequently  to  the  posterior  wall  than  to 
the  anterior.  If  the  fixation  of  the  ovum  is  sufficiently  low,  the  placenta  may 
partly  or  completely  close  the  internal  os,  thus  giving  rise  to  what  is  known  as 
placenta  prcBvia. 

The  Umbilical  Cord. — As  the  amnion  grows  and  extends  ventrally  with 
the  ventral  bending  of  the  embryonic  disk,  the  yolk  stalk  and  sac,  now  very 
much  attenuated,  become  pressed  against  the  cord  of  mesodermal  tissue  which 


FCETAL  MEMBRANES.  129 

connects  the  embryo  with  the  chorion,  and  incorporated  with  it  to  form  the 
umbilical  cord  (Figs.  89  and  90). 

The  umbilical  cord  thus  consists  of:  (Fig.  116) : 

1.  Amnion.     This  is  attached  to  the  embryo  at  the  navel.     It  is  at  first 
loosely  connected  with  the  underlying  tissue  of  the  cord  so  that  it  is  easily 
peeled  off;  later  it  becomes  firmly  adherent.     The  epithelium  of  the  amniotic 
covering  of  the  cord  is  stratified  and  is  described  by  some  (Minot,  McMurrich) 
as  of  embryonic  ectodermic  origin  instead  of  as  part  of  the  amnion. 

2.  What  may  be  called  the  ground  substance  or  substantia  propria  of  the 
cord.     This  is  an  embryonic  connective  tissue  often  described  as  "mucous 

Umbilical  vein 


Amnion 


Allantoic 
stalk 

FIG.  116. — Transverse  section  of  umbilical  cord  of  a  pig  embryo  six  inches  in  length.    Photograph* 

tissue."  It  consists  of  a  soft  gelatinous  intercellular  substance  and  irregular, 
branching  stellate  cells.  On  account  of  its  consistency  it  has  been  called 
"\Yharton's  jelly." 

3.  Three  umbilical  vessels — two  arteries  and  one  vein.  All  these  vessels 
are  thick  walled  and  the  developing  smooth  muscle  is  in  bundles  separated  by 
considerable  connective  tissue.  The  two  umbilical  arteries  carry  venous  blood 
from  the  foetus  to  the  placenta  where  their  branches  ultimately  give  rise  to  the 
capillaries  of  the  chorionic  villi.  From  the  villi  the  blood  enters  the  terminals 
of  the  umbilical  vein  and  returns  as  arterial  blood  to  the  foetus  (Fig.  217). 

As  they  traverse  the  cord  the  arteries  make  a  number  of  spiral  turns  around 
the  vein  and  give  to  the  cord  the  appearance  of  being  spirally  twisted.  The 


130  TEXT-BOOK  OF  EMBRYOLOGY. 

cause  of  this  twisting  is  not  known.  In  places  where  the  turns  are  quite  abrupt 
and  there  are  considerable  accumulations  of  connective  tissue,  the  cord  has  a 
knotted  appearance.  These  points  are  known  as  false  knots.  Rarely  the  cord 
is  actually  tied  into  a  more  or  less  complex  knot — true  knot — probably  due  to 
movements  of  the  foetus. 

4.  Remnants  of  the  allantoic  stalk  and  of  the  yolk  stalk.  These,  if  present, 
are  continuous  or  broken  cords  of  epithelial  cells.  Rarely  one  or  the  other  may 
retain  its  lumen  or  some  of  the  yolk  stalk  vessels  may  remain. 

As  the  yolk  stalk  is  carried  around  to  be  incorporated  as  part  of  the  umbilical 
cord  there  is  enclosed  with  it  a  small  part  of  the  extraembryonic  body  cavity. 

The  human  umbilical  cord  averages  50  cm.  in  length  and  has  a  diameter  of 
about  1.5  cm. 

The  Expulsion  of  the  Placenta  and  Membranes.— After  the  birth  of  the 
child,  the  uterine  contractions  usually  cease  temporarily  and  the  uterine  walls 
remain  contracted  around  the  placenta.  In  the  course  of  a  few  moments  the 
uterine  contractions  are  resumed  and  the  placenta  and  membranes  are  ex- 
pelled as  the  after-birth. 

The  line  of  separation  of  the  placenta  and  of  the  decidua  parietalis  from  the 
uterine  mucosa  is  through  the  deeper  part  of  the  spongy  layer  (Fig.  113).  By 
this  separation  many  blood  vessels  are  opened,  the  hemorrhage  being  con- 
trolled by  the  firm  contractions  of  the  uterine  muscle.  The  condition  of  the 
uterine  mucosa,  after  child-birth,  has  been  described  as  an  exaggeration  of  its 
condition  at  the  end  of  menstruation.  Reconstruction  of  the  mucosa  takes 
place  by  proliferation  of  the  still  remaining  connective  tissue  and  of  the  gland- 
ular elements, 

Anomalies. 

The  manner  in  which  the  placenta  is  formed — by  excessive  development  of 
the  decidua  and  chorion  over  a  limited  area  and  atrophy  of  the  chorion  through- 
out the  remainder  of  its  extent — suggests  the  most  frequent  variations  from  the 
normal. 

The  villi  instead  of  developing  over  the  usual  discoidal  area  may  develop  along 
a  band-like  area  which  more  or  less  completely  encircles  the  chorion.  This  gives 
rise  to  an  annular  placenta  similar  to  that  seen  in  the  Carnivora.  Continued 
development  of  the  villi  over  the  entire  chorion  may  occur.  This  results  in  a 
thin  "placenta  membranacea."  Such  a  placenta  is  apt  to  be  adherent  and  may 
thus  cause  a  serious  postpartum  condition.  Failure  of  the  villi  to  atrophy  and 
their  continued  development  over  more  than  a  single  area  give  rise  to  variations 
in  form  and  number  of  placentae.  When  there  are  two  not  very  distinctly 
separated  areas  the  condition  is  known  as  placenta  bipartita.  Two  completely 
separated  placentae  with  distinct  branchings  of  the  umbilical  vessels  to  supply 


FCETAL  MEMBRANES.  131 

them  are  known  as  placenta  duplex.  Placenta  triplex  and  up  to  placenta  septu- 
plex  have  been  described.  When  one  or  more  placental  lobules  develop  at  a 
little  distance  from  the  main  placental  mass  but  connected  with  the  latter  by 
blood  vessels,  the  result  is  the  not  uncommon  placenta  succenturiata.  Placenta 
spuria  is  applied  to  such  an  accessory  lobule  when  it  has  no  vascular  connection 
with  the  main  placenta  and  consequently  no  function. 

Anomalies  of  the  placenta  associated  with  multiple  pregnancies  and  with 
anomalies  of  the  foetus  will  be  found  under  their  respective  heads. 

Anomalies  of  the  cord  are  for  the  most  part  dependent  upon  anomalies  of 
the  foetus  and  of  the  placenta. 

References  for  Further  Study. 

BEXEKE:  Sehr  junges  menschliches  Ei.  Monatsschr.  f.  Geburtshilfe  u.  Gynakologie,  Bd. 
XXII,  1904. 

BONNET,  R.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Berlin,  1907. 

BRYCE,  T.  H.:  Embryology.     In  Quain's  Anatomy,  nth  ed.,  Vol.  I,  1908. 

BRYCE,  T.  H.,  and  TEACHER,  J.  H.:  An  Early  Ovum  Imbedded  in  the  Decidua. 
Glasgow,  1908. 

CRAGIX,  E.  B.:  Text-book  of  ObstetricG.     1915. 

FRASSI,  L.:  Uber  ein  junges  menschliches  Ei  in  situ.     Arch.f.  mik.  Anat.,  Bd.  LXX,  1907. 

GROSSER,  O.:  Die  Eihaute  und  der  Placenta.     1908. 

HERTWIG,  O.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  und  der  Wirbel- 
tiere.  Berlin,  1906. 

HOFBAUER,  J.:  Biologic  der  menschlichen  Placenta.     Wien  and  Leipzig,  1905. 

HUBRECHT,  A.  A.  W.:  Placentation  of  Erinaceus  Europaeus.  Quart,  Jour,  of  Mic.  Sci.t 
Vol.  XXX,  1889. 

Vox  HUEKELOM,  S.  I  Ueber  die  menschliche  Placentation.  Archiv.  fur  Anat.  und  Physiol., 
Anat.  Abth.,  1898. 

KEFBEL,  F.,  and  MALL,  F.  P.:  Manual  of  Human  Embryology.     Vol.  I,  1910. 

KOLLMAXX,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMAXX,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Bd.  I,  1907. 

LEOPOLD,  G.:  Ueber  ein  sehr  junges  menschliches  Ei  in  situ.     Leipzig,  1906. 

MARCHAXD,  F.:  Beobachtungen  an  jungen  menschlichen  Eiem.  Anat.  Hejte,  Bd.  XXL 
1903. 

McMuRRicH,  J.  P.:  The  Development  of  the  Human  Body.     Philadelphia,  1907. 

MINOT,  C.  S.:  Uterus  and  Embryo.    Jour,  of  MorphoL,  Vol.  II,  1889. 

MIXOT,  C.  S.:  Laboratory  Text  -book  of  Embryology.     Philadelphia,  1903. 

PETERS,  H.:  Ueber  die  Einbettung  des  menschlichen  Eies  und  das  friiheste  bisher 
bekannte  menschliche  Placentationsstadium.  Leipzig,  1899. 

MERTTEXS,  J.:  Beitrage  zur  normalen  und  pathologischen  Anatomic  der  menschlichen 
Placenta.  Zeitschr.  /.  Geburtshilje  u.  Gynakologie,  Bd.  XXX,  XXXI,  1894. 

REJSEK,  J.:  Anheftung  (Implantation)  des  Saugetiereies  an  die  Uteruswand,  insbesondere 
des  Eies  von  Spermophilus  citillus.  Arch.  f.  mik.  Anat.,  Bd.  LXIII,  1904. 

Rossi  DORIA,  T.:  Ueber  die  Einbettung  des  menschlichen  Eies,  studirt  an  einem  kleinen 
Eie  der  zweiten  Woche.  Arch.  f.  Gynak.,  Bd.  LXXVI,  1905. 

SELEXKA,  E.:  Studien  iiber  die  Entwickelungsgeschichte  der  Tiere;  (MenschenatTen) . 
Wiesbaden,  1901-1906.  Parts  8-10. 


132  TEXT-BOOK  OF  EMBRYOLOGY. 

STRAHL,  H. :  Die  Embryonalhiillen  der  Sauger  und  die  Placenta.     In  Hertwig's  Handbuch 
der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere.     Bd.  I,  Teil  II,  1902. 
WEBSTER,  J.  C.:  Human  Placentation.     Chicago,  1901. 


CHAPTER  VIII. 
THE  DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 

The  segmentation  of  the  ovum  and  the  formation  of  the  blastodermic  vesicle 
have  not  been  observed  in  man.  For  these  stages  it  is  necessary,  therefore,  to 
depend  upon  the  lower  Mammals.  In  those  Mammals  in  which  the  processes 
have  been  observed,  the  segmentation  of  the  ovum  produces  a  solid  mass  of 
cells  known  as  the  morula  (Fig.  88;  compare  with  Fig.  33).  The  superficial 
cells  of  the  morula  then  become  differentiated  from  those  in  the  interior.  The 
result  is  a  solid  sphere  composed  of  a  central  mass  of  polyhedral  cells  and  an 
enveloping  layer  of  somewhat  flattened  cells  (Fig.  88;  compare  with  Fig.  33). 
The  cells  of  the  enveloping  layer  become  still  more  differentiated  from  those  of 
the  central  mass,  and  the  sphere  continues  to  increase  in  size  owing  to  the  pro- 
liferation of  both  kinds  of  cells.  The  next  step  in  development  is  the  formation 
of  a  cavity  within  the  sphere.  Among  Invertebrates,  where  but  little  yolk  is 
present  and  where  no  distinct  differentiation  of  the  superficial  cells  occurs,  the 
central  cells  are  displaced,  or  pushed  toward  the  periphery,  so  that  the  morula  is 
changed  into  a  hollow  sphere — the  Uastula — the  wall  of  which  is  composed  of  a 
single  layer  of  cells  (p.  46).  Among  Mammals,  however,  instead  of  a  displace- 
ment of  the  central  cells,  there  appear  within  the  cells  vacuoles  which  continue 
to  enlarge  and  finally  become  confluent,  thus  forming  a  cavity  which  occupies 
the  greater  part  of  the  interior  of  the  sphere.  There  remain  then,  after  the 
vacuolization,  the  enveloping  cells,  or  trophoderm,  and  a  few  of  the  central  cells 
which  are  attached  to  the  trophoderm  over  a  small  area  and  constitute  the 
inner  cell  mass  (Fig.  88).  The  latter  is  the  anlage  of  the  embryonic  body. 
As  stated  on  page  48,  the  cavity  of  the  sphere  in  Mammals  is  not  homologous 
with  the  cavity  of  the  blastula  in  the  lower  forms,  but  the  vacuolization  of  the 
cells  probably  represents  a  belated  and  abortive  attempt  at  yolk  formation. 

Following  the  formation  of  the  yolk  cavity,  those  cells  of  the  inner  cell  mass 
which  border  it  become  differentiated,  proliferate  and  gradually  spread  out  in  a 
single  layer  that  finally  forms  a  complete  lining  for  the  cavity.  The  cells  of  this 
layer  constitute  the  primitive  entoderm  (Fig.  88).  In  the  meantime  some  of  the 
cells  of  the  inner  cell  mass  which  lie  between  the  differentiating  entoderm  and 
the  trophoderm  undergo  a  process  of  vacuolization,  leaving  only  a  single  layer 
closely  applied  to  the  entoderm.  This  layer  is  the  embryonic  ectoderm,  and  the 
newly  formed  cavity  between  it  and  the  trophoderm  is  the  amniotic  cavity 

133 


134  TEXT-BOOK  OF  EMBRYOLOGY. 

(Fig.  89;  compare  with  Fig.  52).     The  further  development  of  the  latter  has 
been  described  on  page  112. 

At  this  stage  the  sphere  contains  two  cavities,  the  larger  yolk  cavity  and  the 
smaller  amniotic  cavity,  separated  by  a  double  layer  of  cells,  the  ectoderm  and 
entoderm,  which  constitute  the  embryonic  disk.  The  greater  part  of  the  wall  of 
the  sphere  is  composed  of  two  layers;  the  portion  forming  the  wall  of  the  larger 
yolk  cavity  being  composed  of  trophoderm  and  entoderm,  the  portion  forming 
the  wall  of  the  smaller  amniotic  cavity  being  composed  of  trophoderm  alone 
(Fig.  89).  The  entire  structure  is  spoken  of  as  the  Uastodermic  'vesicle. 


FIG.  117. — Human  embryo  of  two  months  (twenty-six  millimeters).     Photograph. 
The  embryo  lies  within  the  chorion  (open  on  one  side),  to  which  it  is  attached  at  the  right  of  the 
figure  by  the  umbilical  cord;  around  the  point  of  attachment  the  chorionic  villi  can  be  seen. 
The  amnion  has  been  opened  and  turned  back. 

The  formation  of  the  mesoderm  has  been  discussed  elsewhere  (Chap.  VI, 
p.  81).  At  this  point  it  is  sufficient  to  say  that  it  appears  in  the  wall  of  the 
yolk  cavity  as  a  third  layer  between  the  trophoderm  and  entoderm,  and,  in  the 
embryonic  disk,  between  the  ectoderm  and  entoderm.  Thus  the  blastodermic 
vesicle  possesses  all  three  germ  layers  (Fig.  89). 

In  the  further  course  of  development  the  mesoderm  splits  into  two  layers, 
an  outer  or  parietal  and  an  inner  or  visceral.  Between  the  layers  a  cleft  ap- 
pears, which  is  completely  bounded  by  mesoderm,  on  the  outer  side  by  the 
parietal,  on  the  inner  side  by  the  visceral.  The  parietal  and  visceral  layers 
are  in  apposition  to  the  trophoderm  and  entoderm  respectively.  The  two 
layers  of  mesoderm  soon  become  widely  separated  owing  to  rapid  growth  of 
the  parietal  layer  and  the  trophoderm.  The  parietal  layer  of  mesoderm  and 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


135 


the  trophoderm  together  constitute  the  chorion;  the  original  cavity  of  the 
blastodermic  vesicle  with  its  wall  of  entoderm  and  visceral  mesoderm  is  the 
yolk  sac;  the  newly  acquired  cavity  between  the  chorion  and  yolk  sac  is  the 
extraembryonic  body  cavity  or  exocoelom.  The  embryonic  disk  lies  on  one  side 
of,  and  might  be  said  to  form  the  roof  of  the  yolk  cavity. 

A  very  young  human  embryo  described  by  Peters  (Fig.  83)  corresponds  ap- 
proximately to  the  stage  of  development  shown  in  Fig.  90,  A .     The  entire 

Amniotic  cavity 


Muscular  coat 
of  uterus 


Decidua 

—  parietalis  + 

capsularis 


Cervix 

FIG.  118. — Opened  uterus  containing  membranes  and  foetus  of  three  months.     Length  of 
foetus,  thirty-five  millimeters.     Natural  size.     Bonnet. 

vesicle  measures  about  i  mm.  in  diameter  and  encloses  the  small,  flat  em- 
bryonic disk  with  its  appended  yolk  sac.  The  disk  proper  consists  of  three 
layers  of  cells — the  ectoderm,  mesoderm  and  entoderm.  The  chorion  is  widely 
separated  from  the  yolk  sac  by  the  exoccelom.  See  also  Fig.  106. 

An  embryo  slightly  more  advanced  than  that  described  by  Peters  has  been 
described  by  von  Spec  (Fig.  84) .  In  this  case  a  furrow — the  neural  groove — 
appears  on  the  dorsal  (ectodermal)  side  of  the  embryonic  disk,  and  the  latter  is 


136 


TEXT-BOOK  OF  EMBRYOLOGY. 


somewhat  elongated  in  the  direction  of  the  furrow.  At  the  sides  and  ends  the 
disk  is  bent  ventrally  so  that  a  depression  is  formed  around  it.  The  margin  of 
the  disk  is  continuous  with  the  amnion  and  with  the  yolk  sac  (Figs.  85  and  90, 
B,  C).  The  disk  as  a  whole  shows  a  trace  of  constriction  from  the  yolk  sac, 
but  at  one  end  remains  attached  to  the  chorion  by  means  of  a  mesodermal 
structure — the  belly  stalk  (Fig.  85). 

Still  a  little  further  advanced  than  von  Spec's  embryo,  is  one  described  by 


Cerebral  plate 


Amnion 


Heart 


Ant.  entrance  to 
prim,  gut  (Ant. 
Intest.  portal) 


Post,  entrance  to 
prim,  gut  (Post, 
intest.  portal) 


\    Yolk  sac 
(cut  edge) 


Yolk  sac   ~ 


Neural  tube 


Belly  stalk 


Neural  fold 
Neural  groove 


Neural  fold 


FIG.  119. — (a)  Ventral  view;  (b)  dorsal  view  of  human  embryo  with  8  pairs  of  primitive 

segments  (2.11  mm.).     Eternod.     From  models  by  Ziegler. 

In  b  the  amnion  has  been  removed,  merely  the  cut  edge  showing;  in  a  the  yolk  sac  has 

been  removed. 

Eternod  (Fig.  119).  What  was  originally  the  embryonic  disk  has  here  become 
more  elongated,  and  has  assumed  a  sort  of  cylindrical  shape  owing  to  the  rolling 
under  of  the  lateral  margins.  As  a  part  of  the  rolling  under  process,  the  depres- 
sion which  originally  surrounded  the  disk  has  become  deeper  and  has  effected  a 
still  greater  degree  of  constriction  between  the  cylindrical  body  and  the  yolk 
sac.  The  caudal  end  of  the  body  remains  attached  to  the  chorion  by  means  of 
the  belly  stalk.  The  lips  of  the  neural  groove  have  turned  dorsally  and  fused  in 
the  middorsal  line  along  part  of  their  course. 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


137 


From  a  comparison  of  the  three  stages  which  have  been  mentioned,  it  can  be 
inferred  that  the  process  which  establishes  the  cylindrical  form  of  the  body  is 
essentially  one  of  bending  of  the  margins  of  the  embryonic  disk  with  accom- 
panying elongation  of  the  disk.  It  is  obvious  that  the  process  begins  at  an  early 
period — coincident  with  the  appearance  of  the  primitive  streak  and  neural 
groove.  The  margins  of  the  disk  bend  ventrally  and  form  the  lateral  body  walls 
(Figs.  90,  C,  and  84),  then  bend  inward  and  finally  meet  in  the  midventral  line 
to  form  the  ventral  body  wall.  At  the  same  time  the  body  gradually  be- 
comes elongated  in  the  direction  of  the  neural  groove  (Fig.  119).  When  the 
body  walls  bend  inward  a  constriction  is  produced  between  the  body  and  the 


Fore-brain 


Neural  tube 


Omphalomesenteric 
vein 


Yolk  sac 


Amnion 


fc-   Belly  stalk 


FIG.  1 20. — Dorso-lateral  view  of  human  embryo  with  fourteen  pairs  of  primitive 
segments  (2.5  mm.).     Kollmann. 


yolk  sac.  As  the  body  and  yolk  sac  enlarge,  the  constriction  becomes  relatively 
deeper  until  the  yolk  sac  is  attached  to  the  ventral  side  of  the  body  by  a  slender 
cord — the  yolk  stalk  (Fig.  123).  While  in  the  earlier  stages  there  is  an  active 
bending  of  the  margins  of  the  disk,  in  the  later  stages  the  body  grows  rapidly  in 
size,  especially  in  length,  and  extends  out  beyond  the  yolk  sac  (Fig.  120).  This 
makes  it  appear  that  the  yolk  stalk  is  becoming  smaller.  As  a  matter  of  fact, 
the  diminution  in  the  relative  size  of  the  yolk  stalk  is  more  apparent  than  real, 
the  apparent  diminution  being  caused  largely  by  the  rapid  increase  in  size  of  the 
embryonic  body  and  yolk  sac.  There  is,  however,  a  considerable  distance  where 
fusion  occurs  in  the  midventral  line  as  the  two  lateral  body  walls  meet  to  form 


J38  TEXT-BOOK  OF  EMBRYOLOGY. 

the  ventral  body  wall.  This  line  of  fusion  is  significant  in  its  relation  to  certain 
malformations  (Chap.  XIX). 

Preceding  the  processes  which  establish  the  cylindrical  form  of  the  body, 
there  are  changes  in  the  relation  of  the  amnion  to  the  chorion.  Primarily,  the 
entire  dome-like  roof  of  the  amniotic  cavity  is  attached  to  the  chorion  (Fig.  90,  A) . 
In  further  development,  however,  the  extraembryonic  mesoderm  between  the 
trophoderm  of  the  chorion  and  the  ectoderm  of  the  amnion  splits  farther  back 
over  the  embryo,  leaving  the  latter  attached  at  its  caudal  end  to  the  chorion  by  a 
mass  of  mesoderm— the  so-called  belly  stalk  (Figs.  90,  B,  and  85). 

Following  the  above  mentioned  changes  in  the  amnion,  chorion,  yolk  sac 
and  embryonic  disk,  the  amnion  continues  to  enlarge  and  thus  draws  the  belly 


Cephalic 
flexure 


Branchial  arches 

Branchial  grooves 

Heart 


-^MMB*    mi-  -3n—     Yolk  sac 

Dorsal  flexure 


Amnion    -*" 


Belly  stalk 
Chorion 


FIG.  121. — Human  embryo  2.15  mm.  long.     His. 

stalk  under  the  embryonic  body  and  brings  it  closer  to  the  yolk  sac.  Fir«*!iy,  as 
the  yolk  stalk  becomes  longer  and  more  slender,  the  belly  stalk  and  ytrlk  stalk 
unite  and  become  completely  surrounded  by  the  amnion.  There  is  thu~,  formed 
a  cord-like  structure — the  umbilical  cord — which  is  attached  to  the  veiztral  side 
of  the  body  (Figs.  90,  D,  and  100;  see  also  p.  128). 

The  changes  which  occur  in  the  simple  cylindrical  body,  after  it  is  once 
formed,  consist  of  the  differentiation  of  the  head,  neck  and  body  regions  and  the 
development  of  the  extremities.  Even  in  Eternod's  embryo  (Fig.  119)  the 
cephalic  end  has  become  proportionately  larger  than  the  rest  of  the  body  and 
projects  somewhat  beyond  the  yolk  sac.  This  marks  the  beginning  of  the 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.     139 

head.  The  extreme  end  of  the  head  region  is  bent  ventrally  almost  at  a  right 
angle  to  the  long  axis  of  the  body,  the  bend  being  known  as  the  cephalic  flexure. 
On  the  ventral  side  of  the  body  and  cranial  to  the  attachment  of  the  yolk  sac 
there  is  a  rather  large  protrusion  which  indicates  the  position  of  the  heart. 
Between  the  protrusion  and  the  bent  part  of  the  head  there  is  a  deep  depres- 
sion— the  oral  fossa.  A  series  of  bilaterally  symmetrical  structures  appear  in 
the  body  region  along  the  sides  of  the  neural  tube.  These  are  the  primitive 
segments  (mesodermic  somites). 

All  these  features  are  even  more  clearly  shown  in  Fig.  120,  which  represents 


Cephalic 
flexure 


^^^^^^^^_  Naso-frontal  process 

Maxillary  process -fl 

^B  ^  JSf- Oral  fossa 

Branchial  groove  I 

Branchial  arch  II  ~M  ^— — — —  Mandibular  process 


J_ , —  Ventral  aortic  trunk 

m^ 

Primitive 


Umbilical  vein 


Belly  stalk 
Sacral  flexure 

FIG.  122. — Human  embryo  of  the  third  week.     His. 

an  embryo  2.5  mm.  in  length.  There  is  also  a  further  increase  in  the  size  of 
the  head  region.  A  distinct  concavity,  caused  by  the  dorsal  flexure,  is  seen  in 
the  dorsum  of  the  embryo. 

Another  embryo,  apparently  older  but  only  2.15  mm.  long,  shows  a  re- 
markable exaggeration  of  the  dorsal  flexure  (Fig.  121).  The  middle  part  of  the 
body  seems  to  be  drawn  ventrally  by  the  yolk  sac.  While  this  may  be  a 
normal  feature  at  this  stage,  it  soon  disappears  and  the  concavity  becomes  a 
convexity  (see  p.  140).  A  new  feature  also  appears  in  this  embryo  in  the  form 
of  two  vertical  depressions  just  caudal  to  the  head  region.  These  depressions 


140  TEXT-BOOK  OF  EMBRYOLOGY. 

represent  the  beginning  of  the  branchial  grooves  and  branchial  arches,  which  are 
exceedingly  important  in  the  development  of  the  face  and  neck  regions.  The 
branchial  arches  and  grooves  are  the  morphological  equivalents  of  the  gills 
and  gill  slits  in  lower  Vertebrates  (Fishes,  larvae  of  Amphibians). 

In  an  embryo  somewhat  further  advanced  (Fig.  122)  the  body  as  a  whole 
is  more  robust.  The  heart  is  more  prominent,  and  this  region  is  still  larger  in 
proportion  to  the  body  than  in  the  preceding  stages.  The  dorsal  flexure  is 
much  reduced.  The  cephalic  flexure  is  more  marked  than  in  the  preceding 
stages.  Two  other  flexures  have  appeared — the  cervical  flexure  just  caudal  to 
the  head  region,  the  sacral  flexure  near  the  caudal  end  of  the  body.  All  these 
flexures  together  make  the  embryo  as  a  whole  appear  crescentic  in  form.  The 
primitive  segments  are  at  the  highest  degree  of  their  development  and  extend 
from  the  cervical  flexure  to  the  caudal  end  of  the  body. 

The  two  vertical  depressions  in  the  head  region,  which  were  seen  in  the 
preceding  stage  (Fig.  121),  are  more  prominent  here  as  the  first  and  second 
branchial  grooves  or  clefts.  Just  caudal  to  these  two  other  similar  depressions 
appear  as  the  third  and  fourth  branchial  grooves.  Cranial  to  the  first  groove, 
between  the  first  and  second,  between  the  second  and  third,  and  caudal  to  the 
third  are  elevations  which  mark  the  first,  second,  third  and  fourth  branchial 
arches  respectively.  A  strong  process,  the  maxillary  process,  has  grown 
cranially  from  the  dorsal  part  of  the  first  arch.  The  main  part  of  the  arch  is 
the  mandibular  process. 

In  a  somewhat  later  stage  (Fig.  123)  further  distinct  changes  have  occurred, 
some  of  which  rather  than  leading  toward  the  adult  form  of  the  body  are  de- 
partures from  it.  For  example,  all  the  flexures  have  increased  to  such  an  extent 
that  the  tail  almost  touches  the  head,  the  entire  body  being  decidedly  concave  on 
the  ventral  side.  The  dorsal  flexure,  instead  of  forming  a  concavity  in  the  back, 
now  forms  a  distinct  convexity  and  gives  the  back  a  rounded  appearance.  As  a 
general  rule,  the  tail  at  this  stage  is  bent  to  the  right,  but  in  some  cases  the  bend 
is  toward  the  left. 

The  branchial  arches  and  grooves  are  especially  prominent.  The  fourth 
(and  last)  arch  has  appeared  and  caudal  to  this,  the  fourth  (and  last)  groove. 
The  first  three  arches  have  enlarged  and  become  elongated  so  that  they  almost 
meet  their  fellows  of  the  opposite  side  in  the  midventral  line.  The  site  of 
the  external  ear  is  marked  by  the  second  branchial  groove.  In  addition  to 
this,  the  anlagen  of  the  other  sense  organs  are  apparent.  The  optic  vesicle  is 
seen  just  cranial  to  the  dorsal  end  of  the  first  arch;  the  nasal  fossa  as  a  distinct 
depression  on  the  ventral  side  of  the  head  cranial  to  the  first  arch.  The  yolk 
sac  has  become  so  constricted  at  its  base  that  it  is  now  readily  divisible  into 
the  long,  slender  yolk  stalk  and  the  yolk  sac  or  vesicle. 

On  the  side  of  the  body,  just  caudal  to  the  cervical  flexure,  a  small  protu- 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


141 


berance  forms  the  anlage  of  the  upper  extremity.  This  is  known  as  the  upper 
limb  bud.  A  similar  protuberance  caudal  to  the  sacral  flexure  is  the  lower  limb 
bud. 

Fig.  124  shows  a  stage  slightly  further  advanced  than  Fig.  123.  The  embryo 
as  a  whole  is  more  stocky,  and  the  head  is  still  larger  in  proportion  to  the  rest 
of  the  body.  This  feature  is  especially  noticeable  from  this  stage  up  to  the 
time  of  birth.  The  sacral  and  cervical  flexures  are  still  very  prominent.  The 


Cervical  Cervical 

depression  flexure 


Dorsal  flexure 


Branchial  arch  IV 
Branchial  groove  III 
Branchial  arch  III 
Branchial  groove  II 
Branchial  arch  II 
Branchial  groove  I 
Branchial  arch  I 
Mandibular  process 
Maxillary  process 
Eye 
Nasal  pit 

Heart 
Yolk  stalk 


Lower  limb  bud 


Primitive  segments 


Upper  limb  bud         Liver         Sacral  flexure 
FIG.  123. — Human  embryo  with  twenty-seven  pairs  of  primitive  segments  (7  mm.,  26  days). 


Mall. 


dorsal  flexure,  however,  is  less  prominent  and  the  body  of  the  embryo  is  more 
nearly  straight.  The  sacral  and  cervical  flexures  from  this  time  on  become 
more  and  more  reduced,  while  the  cephalic  flexure,  which  primarily  affects  the 
embryonic  brain,  persists  as  the  mid-brain  flexure  in  the  adult. 

The  branchial  arches  are  actually  no  smaller  but  appear  less  prominent. 
Between  the  mandibular  process  and  the  maxillary  process  there  is  a  distinct 
notch  which  corresponds  to  the  angle  of  ilw  mouth.  The  second  arch  has 
enlarged  at  the  expense  of  the  third  and  fourth,  has  grown  back  over  them  to  a 


142 


TEXT-BOOK  OF  EMBRYOLOGY. 


certain  extent  and  partially  hides  them.  The  nasal  fossa  is  deeper,  and  ex- 
tending from  it  to  the  optic  vesicle  is  a  groove — the  naso-optic  furrow — which 
bounds  the  maxillary  process  on  the  cephalic  side. 

The  tail  (not  clearly  shown  in  the  figure)  is  proportionately  smaller.  It 
does  not  actually  diminish  in  size,  but  the  more  rapid  growth  of  the  body  makes 
it  appear  to  diminish.  The  limb  buds  are  larger  and  a  transverse  constriction 
divides  the  upper  into  a  proximal  and  a  distal  portion.  The  corresponding 
constriction  in  the  lower  limb  bud  has  not  yet  appeared.  The  protrusion  on  the 


Branchial  groove  III 

Branchial  arch  III 

Branchial  groove  II 

Branchial  arch  II 

Branchial  groove  I 

Mandibular  process 

Maxillary  process 

Eye 

Naso-optic  furrow 
Nasal  pit 


Yolk  sac 


Heart 


Lower 
limb  bud 


Liver 


Upper        Umbilical 
limb  bud         cord 


Yolk  stalk 


FIG.  124. — Human  embryo  with  28  pairs  of  primitive  segments  (7.5  mm.).     Photograph. 


ventral  side  of  the  body,  originally  caused  by  the  heart,  is  now  more  prominent 
owing  to  the  fact  that  the  rapidly  growing  liver  also  protrudes  ventrally.  In  this 
particular  case  the  yolk  sac  seems  unusually  large.  The  yolk  stalk  has  become 
enclosed  for  about  half  its  length  within  the  umbilical  cord. 

After  the  stage  just  described  the  dorsal  flexure  becomes  still  less  prominent, 
the  body  of  the  embryo  being  less  curved  (Fig.  125).  The  cervical  flexure 
remains  distinct,  so  that  the  head  is  bent  at  a  right  angle  to  the  long  axis  of  the 
body.  Two  slight  depressions  have  appeared  on  the  dorsum  of  the  embryo— 
the  occipital  depression  just  cranial  to  the  cervical  flexure,  the  cervical  depression 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.     143 

just  caudal  to  the  cervical  flexure.  The  cervical  depression  becomes  more  con- 
spicuous in  later  stages  and  finally  persists  as  the  depression  at  the  back  of  the 
neck  in  the  adult. 

The  maxillary  process  is  more  prominent  than  in  the  preceding  stages,  as  is 
also  the  naso-optic  furrow.  The  second  arch  has  become  larger  and  has  grown 
over  the  third  and  fourth,  thus  completely  hiding  them,  but  a  depression  known 
as  the  preceruical  sinus  is  left  just  caudal  to  the  second  arch.  The  first  branch- 
ial groove  is  relatively  large  and  marks  the  site  of  the  external  auditory  meatus, 
while  the  surrounding  portions  of  the  first  and  second  arches  in  part  are 
destined  to  give  rise  to  the  external  ear. 

Cervical  flexure 
Occipital  depression 


^^^^^  Cervical  depression 

^1 

Cephalic  flexure  

"C  ~\    s 

Dorsal  flexure 


Umbilical  cord 

^/   |K^__X 

\. 

Sacral  flexure 

FIG.  125. — Human  embryo  n  mm.  long  (31-34  days).    His. 

The  distal  portion  of  the  upper  limb  bud  has  become  flattened,  and  four 
radial  depressions  mark  the  boundaries  between  the  digits.  The  lower  limb 
bud  is  now  divided  by  means  of  a  constriction  into  a  proximal  and  a  distal 
portion.  In  development  the  upper  limb  is  always  slightly  in  advance  of  the 
lower. 

The  rotundity  of  the  abdomen,  due  to  the  rapidly  growing  heart  and  liver, 
is  more  pronounced  than  in  the  preceding  stages. 

Fig.  126  shows  a  stage  in  which  the  crescentic  form  of  the  body,  as  seen  in 
profile,  is  not  so  apparent.  This  is  due  principally  to  the  partial  straightening 
of  the  cervical  flexure  and  to  the  greater  rotunditv  of  the  abdomen.  The 


TEXT-BOOK  OF  EMBRYOLOGY. 

cervical  depression  is  deeper,  and  the  neck  region  in  general  is  fairly  well 
differentiated. 

The  ventral  part  of  the  first  branchial  arch  has  fused  with  the  ventral  part 
of  the  second,  leaving  the  dorsal  part  of  the  first  groove  open  to  form  the  ex- 
ternal auditory  meatus.  The  parts  surrounding  the  meatus  bear  more  resem- 
blance to  the  concha  of  the  ear.  The  mandibular  process  of  the  first  arch  has 
become  differentiated  in  part  into  the  lower  Up  and  chin  regions.  The  ventral 
(distal)  end  of  the  maxillary  process  represents  the  region  of  the  upper  lip.  The 


FIG.  126.  FIG.  127. 

FIG.  126. — Human  embryo  of  15.5  mm.  (39-40  days).     His. 
FIG.  127. — Human  embryo  of  16  mm   (42-45  days).     His. 

nose  is  apparent  as  a  short  process  extending  from  the  fore-brain  region  toward 
the  upper  lip. 

The  limb  buds  are  turned  more  nearly  at  right  angles  to  the  long  axis  of  the 
body.  The  radial  depressions  which  were  present  on  the  flattened  distal  por- 
tion of  the  upper  limb  in  the  preceding  stage  are  now  continuous  with  depres- 
sions around  the  distal  border.  Similar  radial  depressions  are  also  present  on 
the  distal  portion  of  the  lower  limb.  The  tail  is  smaller  in  proportion  to  the 
rest  of  the  embryo. 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


145 


After  the  stage  shown  in  Fig.  126  the  cervical  flexure  continues  to  dimm- 
ish, so  that  the  head  comes  to  lie  nearly  in  a  direct  line  with  the  body  (Fig.  127). 
The  rotundity  of  the  abdomen  diminishes  owing  to  the  fact  that  the  heart  and 
liver  grow  more  slowly  relatively  to  the  body  as  a  whole.  The  tail,  which  was 
still  a  prominent  feature  in  Fig.  125,  continues  to  become  less  prominent  in  the 
succeeding  stages  (Figs.  127,  128,  129,  130).  This  is  not  due  so  much  to  an 
actual  atrophy  of  the  tail  as  to  an  increase  in  the  size  of  the  buttocks.  In  the 
adult  the  only  remnant  of  the  tail  is  the  coccyx. 


128. 


FIG.  129. 


FIG.  130. 


FIG.  128. — Human  embryo  of  17.5  mm.  (47-51  days).  His. 
FIG.  129. — Human  embryo  of  18.5  mm.  (52-54  days).  His. 
FIG.  130.— Human  embryo  of  23  mm.  (2  months).  His. 


During  the  second  month  of  development  the  external  genitalia  become  very 
prominent  and  the  sexes  can  be  easily  differentiated. 

By  the  end  of  the  second  month  the  embryo  has  acquired  a  form  which 
resembles  in  a  general  way  the  form  of  the  adult  (Fig.  130).  From  this  time  on 
it  is  customary  to  speak  of  the  growing  organism  as  &  foetus. 

Branchial  Arches — Face — Neck. 

At  a  very  early  stage  (embryos  of  2-4  mm.)  certain  peculiar  structures 
appear  in  that  part  of  the  embryo  which  is  destined  to  become  the  face  and  neck 
regions.  They  are  at  first  noticeable  as  slit-like  depressions  nearly  at  right 
angles  to  the  long  axis  of  the  body.  In  an  embryo  2.15  mm.  long  two  of  these 
depressions  are  visible  (Fig.  121).  Shortly  after  this  a  third  and  then  a  fourth 


146 


TEXT-BOOK  OF  EMBRYOLOGY. 


appears.  At  the  same  time  elevations  appear  between  the  succeeding  depres- 
sions, the  first  elevation  appearing  cranial  to  the  first  depression.  (Compare 
Figs.  122,  123.)  The  elevations  are  the  branchial  arches  and  the  depressions  are 
the  branchial  grooves.  Corresponding  elevations  and  depressions  also  mark  the 


FIG.  131, 


FIG.  132. 


FIG.  131. — Human  embryo  of  78  mm.  (3  months).     Minot. 
FIG.  132. — Human  embryo  of  155  mm.  (123  days).     Minot. 

interior  of  the  pharynx,  so  that  the  portions  of  the  wall  of  the  pharynx  which 
correspond  to  the  grooves  are  thin  as  compared  with  those  portions  which  cor- 
respond to  the  arches. 

The  arches  develop  in  order  from  the  first  to  the  fourth;  consequently  they 
are  successively  smaller  from  the  first  to  the  fourth  (Fig.  122).     The  conditions 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.      147 

change  rapidly,  so  that  in  embryos  of  9-10  mm.,  the  third  and  fourth  arches  have 
sunk  inward,  thus  producing  a  depression  known  as  the  preceruical  sinus. 
Soon  after  this  the  second  arch  enlarges,  grows  over  the  sinus,  and,  fusing  with 
the  underlying  arches,  fills  up  the  depression. 

The  ventral  end  of  the  first  arch  fuses  with  the  ventral  part  of  the  second 
across  the  ventral  part  of  the  first  groove.  The  dorsal  part  of  the  first  groove  is 
thus  left  open  and  becomes  the  external  auditory  meatus.  A  part  of  the  second 
arch,  together  with  a  part  of  the  first  arch  bounding  the  first  groove  on  the 
cranial  side,  is  transformed  into  the  concha  of  the  ear  (Figs.  123,  125,  126). 

The  first  branchial  arch  becomes  the 
largest  and  undergoes  profound  changes 
which  are  extremely  important  in  the  de- 
velopment of  the  face  region.  Earlier  in 
this  chapter  (p.  139)  it  was  stated  that  the 
cephalic  flexure  caused  the  fore-brain  to 
project  ventrally  at  a  right  angle  to  the  long 
axis  of  the  body,  and  that  between  the  pro- 
jecting fore-brain  and  the  heart  a  distinct 
depression  or  pit — the  oral  fossa — was  pres- 
ent. Soon  after  the  appearance  of  the  first 
arch  a  strong  process — the  maxillary  process 
— develops  on  its  cranial  side  (Fig.  122). 
The  main  portion  of  the  arch,  which  may 
be  now  called  the  mandibular  process, 
rapidly  increases  in  size,  extends  ventrally 
and  finally  meets  and  fuses  with  its  fellow 
of  the  opposite  side  in  the  midventral  line 
(Fig.  134).  The  result  of  the  enlargement 
of  the  first  arch  and  its  process  is  that  they 

.  .  .       ,  ,     .        FIG.   133. — Human  embrvo  of  4  months. 

are  interposed  between  the  heart  and  the  Natural  size.    Koiimann. 

fore-brain  vesicle,  thus  bounding  the  oral 

fossa  laterally  (Fig.  122).  During  this  time  the  heart  is  gradually  moving 
caudally.  Meanwhile  a  process — the  naso-frontal  process — grows  ventrally 
from  the  medial  portion  of  the  fore-brain  region  and  comes  in  contact  laterally 
with  the  maxillary  process.  Along  the  line  of  contact  a  furrow  is  left,  which 
extends  obliquely  to  the  region  of  the  optic  vesicle  and  is  known  as  the  naso- 
optic  furrow  (Fig.  134). 

The  various  structures  which  have  been  mentioned  bound  the  oral  fossa 
which  has  become  a  deep  quadrilateral  pit.  Cranially  (above)  the  fossa  is 
bounded  by  the  broad,  rounded,  unpaired  naso-frontal  process;  caudally  (below) 
it  is  bounded  by  the  mandibular  processes;  laterally  it  is  bounded  by  the  maxil- 


148  TEXT-BOOK  OF  EMBRYOLOGY. 

lary  processes,  and  to  a  slight  extent  by  the  mandibular  processes.  Between 
the  maxillary  and  mandibular  processes  on  each  side  a  notch  marks  the  angle 
of  the  mouth. 

As  development  proceeds  these  structures  become  more  elaborate  and  enter 
into  more  intimate  relations  with  one  another.  The  naso-frontal  process 
extends  farther  downward  toward  the  mandibular  processes,  so  that  the 
oral  fossa  becomes  more  nearly  enclosed  and  the  entrance  to  it  reduced  to  a 
crescent-shaped  slit — the  mouth  slit.  At  the  same  time  two  secondary  processes 
develop  on  each  side  from  the  naso-frontal  process.  One  of  these — the 
medial  nasal  process — forms  near  the  medial  line;  the  other — the  lateral  nasal 
process — forms  more  laterally  (Figs.  135, 136).  Between  the  two  processes  there 


Cerebral  hemisphere 

Lat.  nasal  process 
Nasal  pit  • 

Med.  nasal  process  ^^^Bi^^kfl&JB          Naso-optic  furrow 
Angle  of  mouth —M^  ||         Maxillary  process 

Mandibular 


FIG.  134. — Ventral  view  of  head  of  8  mm.  human  embryo.     His. 


is  a  depression — the  nasal  pit — which  marks  the  entrance  to  the  future  nasal 
cavity.  The  maxillary  process  on  each  side  grows  farther  toward  the  medial 
line  and  comes  in  contact  with  the  lateral  and  medial  nasal  processes. 

At  this  stage  all  the  elements  which  enter  into  the  fundamental  structure  of 
the  face  region  are  present.  Further  development  consists  essentially  of 
fusions  between  these  various  elements. 

The  two  medial  nasal  processes  come  closer  together  to  form  the  single 
medial  process  which  gives  rise  to  the  medial  portion  of  the  upper  lip  and  to  the 
adjoining  portion  of  the  nasal  septum.  The  maxillary  process  on  each  side 
fuses  with  the  corresponding  lateral  and  medial  nasal  processes.  This 
fusion  obliterates  the  naso-optic  furrow  and  also  shuts  off  the  communi- 
cation between  the  mouth  slit  and  the  nasal  pit  (Figs.  136,  137).  The  lateral 
nasal  process  gives  rise  to  the  wing  of  the  nose;  the  maxillary  process  gives  rise 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY. 


149 


to  the  major  part  of  the  cheek  and  the  lateral  portion  of  the  upper  lip.  The 
fusion  between  the  maxillary  and  nasal  processes,  as  seen  on  surface  view,  is 
coincident  with  and  a  part  of  J;he  separation  of  the  nasal  cavity  from  the  oral 
cavity  (see  page  319).  The  nose  itself  is  at  first  a  broad,  flat  structure,  but 
later  becomes  elevated  above  the  surface  of  the  face,  with  an  elongation  and  a 
narrowing  of  the  bridge. 


Mid-brain 


Cerebral  hemisphere 

Lat.  nasal  process 
Nasal  pit 

Med.  nasal  process 
Angle  of  mouth 


Eye 

Naso-optic  furrow 

Maxillary  process 


B —  Mandibular  process 


Branchial  grooves 


^B Branchial  arch  II 


FIG.  135. — Ventral  view  of  head  of  113  mm.  human  embryo.     Rabl. 

The  lower  jaw,  lower  lip  and  chin  are  formed  by  the  mandibular  processes  of 
the  first  branchial  arch  (Figs.  134,  136,  137).  At  first  the  chin  region  is  rela- 
tively short,  but  broad  in  a  transverse  direction.  Later  it  becomes  longer  and  a 
transverse  furrow  divides  the  middle  portion  into  lower  lip  and  chin  (Fig.  137). 

The  Extremities. 

The  limb  buds  appear  in  human  embryos  about  the  end  of  the  third  week  as 
small,  rounded  protuberances  on  the  ventro-lateral  surface  of  the  body.  The 
upper  limb  buds  arise  just  caudal  to  the  level  of  the  cervical  flexure,  the  lower 
opposite  the  sacral  flexure  (Figs.  123,  124).  The  upper  appear  first,  the  lower 
following  shortly,  and  the  difference  in  time  in  the  appearance  of  the  upper 
and  lower  buds  is  followed  by  a  difference  in  degree  of  development,  the 
upper  extremities  maintaining  throughout  f cetal  life  a  slight  advance  in  develop- 
ment over  the  lower. 


150 


TEXT-BOOK  OF  EMBRYOLOGY. 


During  the  fourth  week  the  limb  buds  become  elongated,  and  each  bud 
becomes  divided  by  a  transverse  constriction  into  a  proximal  and  a  distal  por- 
tion (Figs.  124,  125).  The  proximal  portion  remains  cylindrical,  while  the 


Nasa  fossa 

Naso-optic  furro 
Mouth  slit 

Branchial  groove  I  """I 


Cerebral  hemisphere 

Naso-frontal  process 
Lateral  nasal  process 
Medial  nasal  process 
Maxillary  process 

Mandibular  process 


FIG.  136. — Ventral  view  of  head  of  13.7  mm.  human  embryo.     His. 

distal  portion  becomes  somewhat  broader  and  considerably  flattened.  Dur- 
ing the  fifth  week  the  digits  appear  (see  below) .  During  the  sixth  week  the 
proximal  portion  of  each  bud  is  subdivided  by  a  transverse  constriction  into 
two  segments  (Fig.  127).  Thus  each  extremity  as  a  whole  is  divided  into  three 


Branchial  groove  I 
(external  ear) 


Nose 

Lat.  nasal  process 
Maxillary  process 

Med.  nasal  process 


FIG.  137. — Ventral  view  of  head  of  human  embryo  of  8  weeks.    His. 

segments — each  upper,  into  arm,  forearm  and  hand,  each  lower,  into  thigh,  leg 
and  foot. 

The  anlagen  of  the  digits  (fingers  and  toes)  appear,  during  the  fifth  week,  in 
the  broader,  flattened  distal  portions  of  the  limb  buds.     The  boundaries  be- 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.     151 

tween  the  anlagen  are  marked  by  radial  depressions  on  the  flat  surfaces;  the 
anlagen  themselves  are  the  elevations  between  the  depressions  (Figs.  125,  126). 
The  anlagen  grow  rapidly  in  thickness  and  length,  thus  producing  not  only  an 
apparent  deepening  of  the  radial  depressions  but  also  indentations  around  the 
distal  free  borders  of  the  limb  buds  (Fig.  126).  The  depressed  areas  produce  a 
web-like  structure  between  the  digits,  resembling  the  web  in  some  aquatic 
animals.  The  web  does  not  keep  pace  with  the  digits,  however,  and  is  soon 
confined  to  the  proximal  ends  of  the  latter.  In  length  the  fingers  grow  slightly 
more  rapidly  than  the  toes  and  thus  become  somewhat  longer.  From  the 
seventh  week  on,  the  thumb  and  great  toe  become  more  and  more  widely  sepa- 
rated from  the  index  finger  and  the  second  toe  respectively  (Figs.  128,  130,  131). 

As  the  limb  buds  become  elongated  during  the  earlier  stages  of  development, 
they  assume  a  position  with  their  long  axes  nearly  parallel  with  the  long  axis  of 
the  body,  and  are  directed  caudally  (Fig.  125).  In  later  stages  they  are  directed 
ventrally  and  their  long  axes  are  nearly  at  right  angles  to  the  long  axis  of  the 
body  (Fig.  126).  The  radial  margins  of  the  upper  extremities  are  turned 
toward  the  head,  as  are  the  tibial  margins  of  the  lower.  The  palmar  surfaces 
of  the  hands  and  the  plantar  surfaces  of  the  feet  are  turned  inward  or  toward 
the  body.  The  elbow  is  turned  slightly  outward  and  toward  the  tail,  the  knee 
slightly  outward  and  toward  the  head.  From  these  conditions  it  may  be  con- 
cluded that  the  radial  side  of  the  upper  extremity  is  homologous  with  the  tibial 
side  of  the  lower;  that  the  palmar  surface  of  the  hand  is  homologous  with  the 
plantar  surface  of  the  foot;  and  that  the  elbow  is  homologous  with  the  knee. 

In  order  to  acquire  the  position  relative  to  the  body  as  found  in  postnatal 
life,  the  extremities  must  undergo  further  changes.  These  consist  essentially 
of  tortions  around  their  long  axes.  The  right  upper  extremity  turns  to  the 
right,  the  right  lower  turns  to  the  left.  The  left  upper  extremity  turns  to  the 
left,  the  left  lower  turns  to  the  right.  At  the  same  time  the  extremities  rotate 
through  an  angle  of  ninety  degrees  and  again  come  to  lie  parallel  with  the  long 
axis  of  the  body.  The  result  is  that  the  radial  sides  of  the  upper  extremities  are 
turned  outward  (away  from  the  sagittal  plane  of  the  body)  and  the  tibial  sides 
of  the  lower  are  turned  inward  (toward  the  sagittal  plane  of  the  body) .  In  the 
upper  extremity  this  is,  of  course,  the  supine  position  in  which  the  radius  and 
ulna  are  parallel. 

Age  and  Length  of  Embryos. 

AGE. — Certain  general  conclusions  regarding  the  age  of  embryos  have  been 
formulated  by  His  (Anatomic  menschlicher  Embryonen,  1882)  and  accepted 
for  the  most  part  by  embryologists.  These  as  stated  by  His  are  as  follows: 

i.  Development  begins  at  the  time  of  impregnation,  that  is,  at  the  moment 
when  the  male  sexual  element  enters  the  ovum  and  fertilizes  it. 


152  TEXT-BOOK  OF  EMBRYOLOGY. 

2.  The  time  the  ovum  leaves  the  ovary  is  determined  by  the  menstrual 
period,  but  the  rupture  of  the  (Graafian)  follicle  is  not  necessarily  coincident 
with  the  beginning  of  hemorrhage;  it  may  occur  two  or  three  days  before  or  it 
may  occur  during  hemorrhage. 

3.  The  egg  is  not  capable  of  being  fertilized  at  any  point  in  its  course  from 
the  ovary  to  the  uterus,  but  only  in  the  upper  part  of  the  oviduct. 

4.  The  spermatozoa  which  have  entered  the  female  sexual  organs  must 
await  the  ovum  in  the  upper  part  of  the  oviduct,  and  can  retain  their  vitality 
here  for  several  days  or  possibly  for  several  weeks;  the  time  of  cohabitation, 
therefore,  does  not  stand  in  direct  relation  to  the  age  of  the  embryo. 

5.  In  the  majority  of  cases  the  age  of  the  embryo  can  be  estimated  from  the 
beginning  of  the  first  menstrual  period  which  has  lapsed.     It  is  possible,  how- 
ever, for  menstruation  to  occur  after  fertilization  of  the  ovum. 

6.  The  age  of  the  embryo  can  be  expressed  thus :  age  =  X  — M,  or  age  = 
X  — M  — 28.  X  is  the  date  of  the  abortion  and  M  is  the  beginning  of  the  last 
menstrual  period.     The  second  formula  is  used  where  it  is  necessary  to  estimate 
from  the  beginning  of  the  first  period  which  has  lapsed. 

There  is  no  doubt  whatever  that  the  age  of  the  embryo  must  be  dated  from 
the  time  of  fertilization  of  the  ovum;  but  owing  to  the  fact  that  the  time  of 
fertilization  of  the  human  ovum  is  not  known,  the  exact  age  cannot  be  deter- 
mined. Even  when  the  date  of  coitus  and  the  time  of  cessation  of  the  menses 
are  known,  the  uncertainty  regarding  the  time  of  ovulation  and  the  time  re- 
quired by  the  spermatozoa  to  reach  the  upper  end  of  the  oviduct  must  be 
taken  into  consideration.  It  is  now  generally  conceded  that  ovulation  and 
menstruation  are  coincident  in  the  majority  of  cases,  but,  on  the  other  hand, 
ovulation  is  known  to  occur  sometimes  independently  of  the  menstrual  periods 
(see  also  p.  29). 

In  addition  to  the  uncertainty  regarding  the  time  when  development 
begins  there  is  also  an  uncertainty  as  to  the  time  when  the  embryo  ceases  to 
develop.  For  in  most  cases  the  embryos  are  abortions  and  the  death  of  the 
embryo  does  not  necessarily  precede  immediately  its  expulsion  from  the  uterus. 

It  is  convenient,  however,  for  practical  purposes,  to  have  some  means  of 
approximating  the  age  of  an  embryo.  His'  formulae  serve  to  determine  the  age 
within  certain  limits.  It  is  obvious  from  these  formulae  that  there  is  a  possibility 
of  an  error  of  twenty-eight  days  in  the  estimate.  Yet  in  the  earlier  stages  of 
development  (during  the  first  three  months)  the  error  can  be  corrected  after 
examination  of  the  embryo,  since  there  is  no  difficulty  in  recognizing  the  differ- 
ence, for  example,  between  an  embryo  two  weeks  old  and  one  six  weeks  old. 

LENGTH.— Many  German  authors  employ  two  different  methods  for 
measuring  embryos  at  different  periods.  One  of  these  methods  they  use 
in  measuring  embryos  between  4  and  14  mm.,  when  the  body  is  much  curved. 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.     153 

The  length  of  the  embryo  is  considered  as  the  length  of  a  straight  line  drawn 
from  the  apex  of  the  cervical  flexure  to  the  apex  of  the  sacral  flexure  (neck- 
rump  length,  Nackensteisslange;  see  Fig.  124).  During  the  second  month  and 
later,  or  in  embryos  of  more  than  20  mm.,  the  body  becomes  more  nearly 
straight  and  the  measurement  is  taken  along  a  straight  line  from  the  apex  of  the 
cephalic  flexure  to  the  apex  of  the  sacral  flexure  (crown-rump  length,  Scheitel- 
steisslange;  see  Fig.  126). 

Owing  to  the  changes  in  curvature  of  embryos  during  development,  no 
one  system  of  measurement  will  give  uniform  results  for  all  stages.  In  this 
country  it  is  the  general  practice  to  measure  the  greatest  length  of  the  embryo, 
in  its  natural  attitude,  along  a  straight  line.  The  measurement  does  not 
of  course  include  the  extremities.  At  certain  stages  this  length  corresponds 
with  the  neck-rump  length,  at  other  stages  with  the  crown-rump  length,  at  still 
other  stages  with  neither. 

RELATION  OF  AGE  TO  LENGTH. — Not  infrequently  the  history  of  an  embryo 
is  not  obtainable,  and  in  such  cases  the  age  must  be  inferred  from  wrhat  is  known 
concerning  the  relation  of  the  age  to  the  length  of  the  embryo.  The  age  can  be 
computed  approximately  by  this  means,  although  there  is  a  possibility  of  error. 
Embryos  of  the  same  age  are  not  necessarily  of  the  same  length,  since  conditions 
of  nutrition,  etc.,  determine  not  only  the  size  of  the  embryo  but  also  the  degree 
of  its  development.  In  the  later  stages  of  development  the  limit  of  error  is  not 
so  important,  but  in  the  younger  stages  the  difference  of  a  day  or  two  means 
much. 

His  estimated  the  ages  of  a  number  of  embryos  from  available  data  as 
follows : 

Embryos  of  2-2  J  weeks  measure  2.2-3  mm.  (neck-rump  length). 

Embryos  of  2^-3  weeks  measure  3-4.5  mm.  (neck-rump  length). 

Embryos  of  3^  weeks  measure  5-6  mm.  (neck-rump  length). 

Embryos  of  4  weeks  measure  7-8  mm.  (neck-rump  length). 

Embryos  of  4j  weeks  measure  10-11  mm.  (neck-rump  length). 

Embryos  of  5  weeks  measure  13  mm.  (neck-rump  length). 

More  recent  researches  on  the  rate  of  development  in  the  lower  Mammals 
tend  to  show  that  development  proceeds  relatively  slowly  during  the  earliest 
stages,  and  then  goes  on  with  increasing  rapidity  for  a  time.  In  the  rabbit,  for 
example,  it  has  been  shown  that  the  embryonic  disk  is  but  slightly  differentiated 
at  the  seventh  and  eighth  days,  while  at  the  tenth  day  the  embryo  possesses 
branchial  grooves  and  primitive  segments.  If  this  peculiarity  in  the  rate  of 
development  occurs  in  the  human  embryo,  the  ages  assigned  to  the  earlier 
embryos  by  His  must  be  increased. 

Mall's  formulae  for  estimating  age,  deduced  from  observations  on  a  large 
number  of  embryos,  are  as  follows:  In  embryos  of  i-ioo  mm.  the  age  in  days 


154 


TEXT-BOOK  OF  EMBRYOLOGY. 


can  be  expressed  fairly  accurately  by  the  square  root  of  the  length  multiplied  by 
100  (Jlength  in  mm.  x  100).  In  embryos  between  100  and  220  mm.  the  age 
in  days  is  about  the  same  as  the  length  in  millimeters. 

Some  of  the  most  important  embryos  which  have  been  described  are 
listed  in  the  accompanying  table,  no  pretense  being  made  of  giving  a  complete 
list.  The  table  is  compiled  largely  from  the  more  extensive  tables  of  Mall 
and  merely  serves  to  indicate  some  of  the  younger  embryos  with  fairly  well- 
known  histories,  from  which  certain  conclusions  have  been  drawn  concerning 
the  relation  of  age  to  length.  The  periodicals  in  which  descriptions  may  be 
found  are  given  with  the  authors'  names  in  " References  for  Further  Study" 
at  the  end  of  this  chapter. 


No. 

Observer 

Dimensions    of    chori- 
onic  vesicle  in 
millimeters 

Number 
of  days  be- 
tween last 
menstrual 
period  and 
abortion 

Number  of  days 
between  first 
lapsed  period 
and  abortion 

Probable 
age  in  days 

Length  of 
embryo  in 
millimeters 

i 

2 

Bryce-Teacher 
Leopold 

1.9  x  i.i  x  .95  
i  4  x   9  x  8   . 

38  

10  

13-14  

0-15  

3 

Peters  
Reichert 

3.  xi.  5  xi.  5  

r   r  v  -7   3 

3°  

A  2 

14. 

Id 

0.19  

5 
6 

von  Spec  
Mall 

7-5X.5-5  

IO  C.  X  7    X  7 

35  

4.1 

1  1 

12  

1  1 

°-37  
08 

7 

Eternod 

10  8  x  8  2  x  6 

J    -3     .   , 

8 

von  Spee 

10  x  8  *\  x  6  5 

•y  r 

I  2 

1   e  i 

Mall 

18  x  18  x  8 

4.1 

I  3 

I  7 

21       

10 

ii 

Thomson  
His 

5-7  

I  C  X  I  2   5J 

42  

4O 

14  
I  2 

14  

12     

2.1  

2   I  <..  . 

12 

Thomson 

15  x  10 

14- 

14     

2.Z.  .  . 

13 
14 

von  Spee.  
Janosik 

i5x  H  
8                         

42  

4.-J 

14  

If     . 

14  
T.Z.  . 

2.69  

1C 

His  

14  x  ii    

48    

2O    

2O  

3.2  

16 

Mall 

24  x  16  x  9 

4.2 

14. 

4 

17 

His 

•JQ  X  2< 

C  I 

2? 

18 

His 

2C  x  2O 

21 

21 

r    . 

10 

M^eyer 

22 

18 

18 

r  2      . 

20 
21 

Stubenrauch  .  . 
Mall         .    . 

2H  X  2< 

45  

ET2 

17  
24     

17  
24  .... 

6  

7.  . 

22 

His  

21  X  17                       

C7 

20  (?) 

27    . 

7  7  c  

23 

Meyer  

4C 

28  

28  

8    

24 

Ecker  

60  

2,2.     . 

32.  . 

IO  

2S 

His  

30  x  27 

61  

22.   . 

73  

II  

26 

His  

35x28  

61  

35  

35   

13-6  

Normal,  Abnormal  and  Pathological  Embryos. 

In  the  majority  of  cases  of  spontaneous  abortion  it  is  not  possible  to  examine 
the  uterus;  but  in  those  cases  where  it  is  possible,  examination  frequently  shows 
abnormal  or  pathological  conditions.  As  might  be  expected,  the  embryos 
obtained  from  abnormal  or  pathological  uteri  very  frequently  show  anom- 
alous conditions  or  pathological  changes,  or  both.  Since  many  of  the 


DEVELOPMENT  OF  THE  EXTERNAL  FORM  OF  THE  BODY.      155 

human  embryos  obtained  are  the  results  of  spontaneous  abortions,  there  is 
reason  to  suspect  that  such  embryos  are  not  normal.  To  the  physician,  as 
well  as  to  the  embryologist,  it  is  important,  therefore,  that  there  should  be  some 
criteria  for  differentiation  between  normal  and  abnormal  or  pathological 
embryos. 

Gross  anomalies,  or  monstrosities,  such  as  cases  in  which  the  head  or  some 
other  member  of  the  body  is  lacking,  or  in  which  the  head  is  disproportionately 
large  or  disproportionately  small,  or  in  which  two  embryos  are  directly  united, 
or  in  which  the  foetal  membranes  are  partially  lacking,  or  in  which  the  mem- 
branes are  present  and  the  embryo  wholly  or  partially  lacking,  and  many  other 
anomalous  conditions,  can,  of  course,  be  recognized  at  once.  Extensive 
pathological  changes  or  processes  of  disintegration  in  the  tissues  of  the  em- 
bryo or  foetal  membranes  are  also  easily  recognized.  But  there  are  many  less 
obvious  anomalies  and  pathological  conditions  which,  nevertheless,  are  im- 
portant. Such  cases  are  most  difficult  to  differentiate. 

The  fcetal  membranes  not  infrequently  are  useful  in  determining  whether 
an  embryo  has  followed  the  normal  course  of  development.  During  the  first 
month  the  amnion  invests  the  embryo  rather  closely  when  development  is 
normal.  If  the  amniotic  sac  is  disproportionately  large,  however,  it  is  a  mark 
of  abnormal  or  pathological  changes.  In  some  cases  an  amniotic  sac  50  to  60 
mm.  in  diameter  contains  an  embryo  but  a  few  millimeters  in  length.  In  the 
earlier  stages  of  development,  before  the  amnion  enlarges  sufficiently  to  reach 
the  chorion,  there  is  present  a  delicate  network  of  fibrils,  the  magma  reticulare, 
which  is  attached  to  both  chorion  and  amnion  and  which  serves  as  a  sort  of 
anchor  for  the  amnion.  In  abnormal  or  pathological  cases  the  magma  reticu- 
lare may  become  wholly  or  partially  fluid  or  granular,  or  may  become  greatly 
increased  in  amount.  It  may  even  extend  through  the  amnion  and  reach  the 
embryo  itself. 

Normal  human  as  well  as  other  mammalian  embryos  in  the  fresh  condition 
are  more  or  less  transparent,  and  such  structures  as  the  heart,  the  larger  blood 
vessels,  the  liver,  and  the  brain  vesicles  can  be  seen  through  the  skin.  If  the 
embryo  has  been  dead  for  some  time  or  has  undergone  pathological  or  degen- 
erative changes,  the  transparency  is  lost. 

Where  pathological  or  degenerative  changes  in  the  embryo  or  its  membranes 
are  suspected  but  cannot  be  definitely  determined  by  macroscopic  examination, 
recourse  may  be  had  to  sectioning  and  staining. 

References  for  Further  Study. 

VAX  BEXEDEX,  E.:  Recherches  sur  les  premiers  stades  du  developpement  du  Murin 
(Vespertilio  murinus).  Anat.  Anz.,  Ed.  XVI,  1899. 

BRYCE,  T.  H.  and  TEACHER,  J.  H.:  AD  Early  Human  Ovum  Imbedded  in  the  Decidua. 
Mac  Lehose  &  Sons,  Glasgow,  1908. 


156  TEXT-BOOK  OF  EMBRYOLOGY. 

ECKER,  A.:  Beitrage  zur  Kenntniss  der  ausseren  Formen  jiingster  menschlichen  Embryo- 
nen.  Archiv.  f.  Anat.  u.  PhysioL,  Anat.  Abth.,  1880. 

ETERNOD,  A.  C.  F.:  Communication  sur  un  oeuf  avec  embryon  excessivernent  jeune. 
Arch.  ital.  de  Biol.  SuppL  12  et  14,  1894. 

ETERNOD,  A.  C.  F.:  Sur  un  oeuf  humain  de  16.3  mm.  avec  embryon  de  2.1  mm.  Arch, 
des.  sci.  phys.  et  nat.t  Vol.  II,  1896. 

His,  W. :  Anatomic  menschlicher  Embryonen.     With  Atlas.    1880-1885. 

His,  W.:  Die  Entwickelung  der  menschlichen  und  tierischen  Physiognomien.  Arch.  /. 
Anat.  u.  PhysioL,  Anat.  Abth.,  1892. 

jAN6siK,  J.:  Zwei  junge  menschliche  Embryonen.     Arch.  /.  mik.  Anat.,  Bd.  XXX,  1887. 

KEIBEL,  F.:  Ein  sehr  junges  Menschliches  Ei.  Arch.  f.  Anat.  u.  PhysioL,  Anat.  Abth., 
1890. 

KEIBEL,  F.:  Entwickelung  der  ausseren  Korperform  der  Wirbeltierembryonen.  In 
Hertwig's  Handbuch  der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere.  Bd.  I, 
Teil  I,  1906. 

KEIBEL,  F.,  and  ELZE,  C.:  Normentafcl  zur  Entwickelungsgeschichte  des  Menschen. 
Jena,  1908. 

KEIBEL,  F.,  and  MALL,  F.  P.:   Manual  of  Human  Embryology.     Vol.  I,  1910. 

KOLLMANN,  J. :  Die  Korperform  menschlicher  normaler  und  pathologischer  Embryonen. 
Arch.  f.  Anat.  u.  PhysioL,  Anat.  Abth.  SuppL,  1889. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1907. 

LEOPOLD,  G.:  Ueber  ein  sehr  junges  menchliches  Ei.     Leipzig,  1906. 

MALL,  F.  P.:  A  Human  Embryo  Twenty-six  Days  Old.  Jour,  of  MorphoL,  Vol.  V, 
1891. 

MALL,  F.  P.:  A  Human  Embryo  of  the  Second  Week.     Anat.  Anz.,  Bd.  VIII,  1893. 

MALL,  F.  P. :  Human  Embryos.  Wood's  Reference  Handbook  of  the  Medical  Sciences, 
Vol.  Ill,  1901. 

MEYER,  H.:  Die  Entwickelung  der  Urnieren  beim  Menschen.  Arch.  f.  mik.  Anat.,. 
Bd.  XXXVI,  1890. 

PETERS,  H.:  Ueber  die  Einbettung  des  menschlichen  Eies,  und  das  fruheste  bisher 
bekannte  menschliche  Placentarstadium.  Leipzig  und  Wien,  1899. 

RABL,  C.:  Die  Entstehung  des  Gesichtes.     I.  Heft.     Leipzig,  1902.     Folio. 

REICHERT,  B.:  Beschreibung  einer  fruhzeitigen  menschlichen  Frucht.  Abhandl. 
preuss.  Akad.,  Berlin,  1873. 

SELENKA,  E.:  Studien  iiber  die  Entwickelungsgeschichte  der  Tiere;  (Menschenaffen). 
Wiesbaden,  1908.  Parts  8  to  10. 

VON  SPEE,  GRAF:  Beobachtungen  an  einer  menschlichen  Keimscheibe  mit  offener 
Medullarrinne  und  Canalis  neurentericus.  Arch.  f.  Anat.  u.  PhysioL,  Anat.  Abth.,  1889. 

VON  SPEE,  GRAF:  Ueber  friihe  Entwickelungsstufen  des  menschlichen  Eies.  Arch.  /, 
Anat.  u.  PhysioL,  Anat.  Abth.,  1896. 

STUBENRAUCH:  Inaug.     Dissert.     Miinchen,  1889. 

THOMPSON,  A.:  Contributions  to  the  History  of  the  Structure  of  the  Human  Ovum 
Before  the  Third  Week  after  Conception,  with  a  Description  of  Some  Early  Ova.  Edin- 
burgh Med.  and  Sur g.  Journal,  Vol.  Ill,  1839. 


PART  II. 


ORGANOGENESIS. 


CHAPTER  IX. 

THE  DEVELOPMENT  OF  THE  CONNECTIVE  TISSUES  AND  THE 

SKELETAL  SYSTEM. 

All  the  connective  or  supporting  tissues  of  the  body,  except  neuroglia, 
are  derived  from  the  mesoderm.  This  does  not  imply,  however,  that  all  the 
mesoderm  is  transformed  into  connective  tissues;  for  such  structures  as  the 
endothelium  of  the  blood  vessels  and  lymphatic  vessels,  probably  blood  itself, 
the  epithelium  lining  the  serous  cavities,  smooth  and  striated  muscle,  and  a  part 
of  the  epithelium  of  the  urogenital  system  are  derived  from  mesoderm. 


Primitive  groove 


Ectoderm 


Mesoderm 


Entoderm 


FIG.  138. — Transverse  section  of  chick  embryo  of  27  hours'  incubation.     Photograph. 

The  origin  of  the  mesoderm  itself  has  been  discussed  elsewhere  (p.  81). 
In  this  connection  it  is  sufficient  to  recall  that  it  is  situated  between  the  ectoderm 
and  entoderm  and  consists  of  several  layers  of  closely  packed  cells  (Fig.  138). 
The  axial  portion  in  the  neck  and  body  regions  becomes  differentiated  into  the 
mesodermic  somites.  At  the  same  time  a  cleft  (the  ccelom)  separates  the  more 
peripheral  portion  into  a  parietal  and  a  visceral  layer  (Figs.  139  and  141).  In 
the  head  region  where,  in  the  higher  animals,  there  is  little  or  no  indication  of 

161 


162 


TEXT-BOOK  OF  EMBRYOLOGY. 


Ectoderm 


Ectoderm 


Coelom 


FIG.  139. — Transverse  section  of  chick  embryo  (2  days'  incubation).     Photograph. 
The  parietal  mesoderm   (lying  above  the  ccelom)   is  not  labeled.     The  two  large  vessels  under 
the  primitive  segments  are  the  primitive  aortae.     Spaces  separating  germ  layers  are  due  to 
shrinkage. 


Mesoderm 
(mesenchyme) 


Neural  tube 


Ectoderm 


Pharynx 


Entoderm 


FIG.  140. — Transverse  section  through  head  region  of  chick  embryo  of  42  hours' 
incubation.     Photograph. 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


163 


somites  and  ccelom,  the  mesoderm  simply  fills  in  the  space  between  the  ecto- 
derm and  entoderm  (Fig.  140).  Portions  of  the  mesoderm  in  all  these  re- 
gions are  destined  to  give  rise  to  connective  tissues.  Each  mesodermic  somite 
soon  becomes  differentiated  into  three  parts — the  sclerotome,  cutis  plate  and 
myotome  (Fig.  142).  Of  these,  only  the  sclerotome  and  cutis  plate  are  directly 
concerned  in  the  formation  of  connective  tissues,  the  myotomes  giving  rise  to 
striated  voluntary  muscle.  The  sclerotomes  are  destined  to  give  rise  to  the 


Neural  tube 


Intermediate 
cell  mass 


Notochord    j 

Entoderm      .<t^w       f^\ 

^r\"C_ 


f    T  •!•£ 

•-^L __ *. 


Visceral  mesoderm  — 


Primitive  segment 


Intermediate 
cell  mass 


I — •     Ectoderm 


Parietal 
mesoderm 


v-"*  ffg)      Lateral 
*~(jf~~  body  wall 


Mesothelium 


Umbilical  vein 


FIG.  141. — Transverse  section  of  human  embryo  with  13  primitive  segments;  section  taken 
through  the  6th  segment.     Kollmann. 

vertebrae  and  other  forms  of  connective  tissue  in  their  neighborhood,  the  cutis 
plates  to  a  part,  at  least,  of  the  corium  of  the  skin.  The  parietal  and  visceral 
layers  of  the  mesoderm  (except  the  mesothelium  lining  the  ccelom)  and  the 
mesoderm  of  the  head  region  are  destined  to  give  rise  to  the  various  types  of 
connective  tissue  forming  parts  of  the  other  organs  of  the  body. 

HISTOGENESIS. 

The  sclerotomes  and  cutis  plates  at  first  constitute  parts  of  the  mesoaermic 
somites,  and  are  composed  of  epithelial-like  cells  with  little  intercellular  sub- 
stance. The  intercellular  substance  gradually  increases  in  amount  so  that  the 


164 


TEXT-BOOK  OF  EMBRYOLOGY. 


Myotome 


Pronephros - 


Parietal  mesoderm— 
Intestine 


Umbilical 

Vein 


Visceral  mesoderm 


FIG.  142. — ^Transverse  section  of  human  embryo  of  the  3rd  week.     Sc/.1,  Break  in  myotome  at 
point  where  sclerotome  is  closely  attached.     Kollmann. 


Neural  tube   — 


Intersegmental 
artery 


Intersegmental 
artery 


Ectoderm 


Sfc/i/^  Sclerotome 


Myocoel 


FIG.  143. — Three  primitive  segments  from  sagittal  section  of  human  embryo  of 
the  3rd  week.     Kollmann. 


THE   CONNECTIVE  TISSUES  AND   THE   SKELETAL  SYSTEM.  165 

cells  become  more  widely  separated  from  one  another,  at  the  same  time 
assuming  oval  or  spindle  shapes  and  then  irregular  branching  forms  (Fig. 
144).  The  rest  of  the  mesoderm,  except  the  mesothelium,  also  undergoes  a 
similar  transformation  so  that  structurally  its  cells  are  indistinguishable  from 
those  derived  from  the  sclerotomes  and  cutis  plates. 

Thus  the  mesoderm  at  this  stage  is  composed  of  irregular,  branching 
cells,  with  a  relatively  large  amount  of  homogeneous  intercellular  substance 
filling  the  interstices.  The  branches,  or  protoplasmic  processes,  of  each 
cell  anastomose  freely  with  those  of  other  cells  in  the  immediate  vicinity. 


I 


FIG.  144.  —  Mesenchymal  tissue  from  somatopleure  of  a  5  mm.  human  embryo. 
Mesothelium  is  shown  along  lower  border  of  figure. 

In  this  manner  a  syncytium  is  formed  to  which  the  term  mesenchyme  is  ap- 
plied (Fig.  144).  The  mesenchyme  itself  lacks  specialization,  being  what 
is  known  as  an  indifferent  tissue,  but  it  constitutes  the  structural  basis  upon 
which  all  the  connective  tissues  of  the  adult  body  are  built  ;  all  the  forms  of 
connective  tissue  (except  neuroglia)  develop  from  it. 

That  intercellular  substance  is  derived  originally  from  the  cell  can  scarcely 
be  denied.  All  the  cells  of  the  organism  are  derived  from  the  fertilized  ovum. 
As  soon  as  two  or  more  cells  are  formed  by  segmentation  of  the  ovum,  they  are 
either  simply  in  apposition  or  else  they  are  united  by  something  in  the  nature 
of  a  "  cement"  substance  which  must  have  been  derived  from  the  cells  them- 
selves. In  the  mesenchymal  tissue  this  intercellular  ground  substance  is  a 
prominent  feature,  and  probably  represents  in  part  nutritive  materials  and 
in  part  the  products  of  cell  activity. 


166 


TEXT-BOOK  OF   EMBRYOLOGY. 


Fibrils  and  Fibers. — The  least  differentiated  and  perhaps  the  least 
specialized  tissue  derived  from  mesenchyme  is  reticular  tissue,  such  as  that 
found  in  the  lymph  nodes  and  spleen.  In  the  peripheral  part  of  the  cyto- 
plasm, or  exoplasm,  of  the  mesenchymal  cells  and  their  processes  there  arise 
delicate  fibrils,  often  extending  from  one  cell  to  another,  which  probably 


FIG.  145. — Fibril  forming  cells  from  fresh  subcutaneous  tissue  of  head  of  chick  embryo.     Boll. 

represent  specialized  parts  of  the  spongioplasm.  These  fibrils  maintain 
their  intracellular  position  instead  of  becoming  separated  from  the  parent 
cytoplasm,  so  that  the  reticular  tissue  retains  a  marked  resemblance  in 
form  to  the  original  mesenchyme. 


FIG.  146. — Connective  tissue  (mesenchymal)  cells  from  larval  salamander.     Flemming. 

The  first  step  in  the  development  of  the  true  fibrillar  forms  of  connective 
tissue  from  mesenchyme  is  the  formation  of  fibrils  and  fibers.  While  it  has 
been  held  by  some  investigators  that  the  fibrils  arise  in  and  from  the  homo- 
geneous intercellular  substance,  the  best  substantiated  view  is  that  they  arise 
within  and  from  the  cytoplasm  of  the  mesenchymal  cells  (Figs.  145  and  146). 
They  then  become  separated  from  the  cytoplasm  and  lie  free  in  the  " ground" 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


167 


substance  in  bundles  (fibers).  These  fibrillated  fibers  are  collaginous  in 
character.  Elastic  fibers,  while  not  fibrillated,  probably  have  a  similar 
origin.  This  first  step  in  development  gives  rise  to  a  loose,  delicate  tissue 
in  the  embryo,  known  as  embryonal  connective  tissue,  from  which  all  the 
adult  forms,  except  reticular  tissue,  develop. 

The  areolar  tissue  of  the  adult  retains  many  of  the  general  characters  of 
embryonal  connective  tissue.  The  fibers,  both  collaginous  and  elastic,  are 
loosely  arranged  and  extend  in  all  directions.  The  cells  (fibroblasts)  are 
fewer,  however,  and  while  they  are  characterized  by  irregular,  branching 
forms  it  is  not  known  whether  their  processes  anastomose. 


FIG.  147. — Longitudinal  section  of  developing  ligament  from  finger  of 
human  foetus  of  6  months.     Photograph. 

In  any  fibrous  tissue,  such  as  areolar,  or  the  denser  forms  (fascia,  tendons, 
ligaments),  the  structure  depends  upon  the  secondary  arrangement  of  the 
fibers  and  not  upon  any  peculiarity  of  origin.  In  all  these  forms  the  fibers 
have  the  same  origin,  but  in  the  denser  fascia,  tendons  and  ligaments  they 
become  arranged  in  parallel  lines  (Fig.  147). 

Adipose  Tissue. — Adipose  tissue  is  a  form  of  connective  tissue  in  which 
the  fatty  element  replaces  to  a  great  extent  the  cytoplasm  in  many  of  the 
embryonic  connective  tissue  cells.  It  always  develops  in  close  relation  to  blood 


168  TEXT-BOOK  OF  EMBRYOLOGY. 

vessels,  and  first  appears  in  the  axilla  and  groin  about  the  thirteenth  week. 
It  is  formed  in  other  places  at  later  periods,  even  during  adult  life,  but  the 
mode  of  development  is  always  the  same.  In  some  of  the  cells  in  the  neigh- 
borhood of  small  blood  vessels  minute  droplets  of  fat  are  deposited.  The 
origin  of  the  fat  is  not  known.  The  droplets  become  larger,  other  smaller  ones 
appear,  and  finally  all  of  them  coalesce  to  form  a  single  large  drop  which  practi- 
cally fills  the  cell.  The  result  of  this  is  that  the  remaining  cytoplasm  is  pushed 
outward  and  forms  a  sort  of  pellicle  around  the  fat.  The  nucleus  also  is 
crowded  outward  and  comes  to  lie  flattened  in  the  pellicle  of  cytoplasm  (Fig. 


Small  artery 

FIG.  148. — Developing  fat  from  subcutaneous  tissue  of  pig  embryo  5  inches  long.  Small 
artery  breaking  up  into  capillary  network'  groups  of  fat  cells  developing  in 
embryonic  connective  tissue 

149) .  At  the  same  time  the  whole  fat  cell  increases  in  size  and  forms  a  relatively 
large  structure. 

Fat  cells  usually  develop  in  groups  or  masses  around  blood  vessels  (Fig. 
148).  The  neighboring  groups  gradually  enlarge  and  approach  each  other, 
but  do  not  fuse,  thus  leaving  more  or  less  fibrous  connective  tissue  between 
them,  which  constitutes  the  interlobular  tissue  seen  in  adult  adipose  tissue. 
Among  the  individual  cells  in  a  lobule  there  is  also  a  small  amount  of  fibrous 
tissue  present.  From  the  mode  of  development  a  small  artery  usually  affords 
the  blood  supply  for  each  lobule. 

Cartilage. — In  the  different  kinds  of  cartilage  the  matrix  probably  repre- 


THE   CONNECTIVE   TISSUES   AND   THE   SKELETAL  SYSTEM. 


169 


sents  a  modification  of  the  "ground  substance"  of  the  original  embryonic 
tissue.  The  fibers  in  the  matrix  are  probably  derived  from  the  cells  in  the 
same  manner  as  the  fibers  in  the  fibrillar  forms  of  connective  tissue  (Fig.  150). 
Osseous  Tissue. — Here  again  the  basis  for  development  is  embryonic 
connective  tissue,  although  in  one  type  of  development  cartilage  precedes  the 
bone.  Two  types  of  ossification  are  recognized — intramembranous  and  intra- 
cartilaginous  or  endochondral.  In  intramembranous  ossification  calcium  salts 
are  deposited  in  ordinary  embryonic  connective  tissue.  In  intracartilagi- 


Capillary 


Embryonic 
connective  tissue 


Arteriole 


FIG.  149. — Developing  fat  from  subcutaneous  tissue  of  pig  embryo  5  inches  long.  Fat  (stained 
black)  developing  in  embryonic  connective  tissue  cells.  At  the  right  are  five  individual  cells 
showing  stages  of  development  from  an  embryonic  cell  to  an  adult  fat  cell. 


nous  ossification  hyalin  cartilage  first  develops  in  the  same  general  shape  as 
the  future  bone  and  the  calcium  salts  are  afterward  deposited  within  the  mass  of 
cartilage.  It  is  customary  to  speak  also  of  another  type  of  ossification — sub- 
periosteal — in  which  the  calcium  salts  are  deposited  under  the  periosteum. 

INTRAMEMBRANOUS  OSSIFICATION. 

This  is  the  type  of  ossification  by  which  many  of  the  flat  bones  of  the  skull 
and  face  are  formed.  The  region  in  which  these  bones  are  to  develop  consists 
of  embryonic  connective  tissue.  At  certain  points  in  this  region  bundles  of 
connective  tissue  fibers  become  impregnated  with  calcium  salts.  Such  areas  are 
known  as  calcification  centers.  In  each  of  these  areas  the  cells  increase  in  num- 
ber, the  tissue  becomes  very  vascular  and  some  of  the  cells,  becoming  more  or 
less  round  or  oval,  with  distinct  nuclei  and  a  considerable  amount  of  cytoplasm, 


170 


TEXT-BOOK  OF  EMBRYOLOGY. 


Ectoplasm  with  t£ 
"white"  fibers     ^  "-•- 


Ground 
substance ' 


Ectoplasm  /     . 


FlG.  150. — Connective  tissue  cells  from  intervertebral  disk  of  calf  embryo;  showing  origin  of 
"white"  and  elastic  fibers  in  protoplasm  of  cells.  Ectoplasm  represents  a  modified  part 
of  the  protoplasm.  Hansen. 


Osteogenetic 
tissue 


FIG.  151. — Vertical  section  through  frontal  bone  of  human  fcetus  of  4  months. 
(Intramembranous  ossification.)     Photograph. 


THE   CONNECTIVE  TISSUES  AND  THE   SKELETAL  SYSTEM.  171 

arrange  themselves  in  single,  fairly  regular  rows  along  the  bundles  of  calcified 
fibers.  The  differentiated  cells  are  known  as  osteoblasts  (bone  formers),  and  the 
whole  tissue  is  now  known  as  osteo genetic  tissue.  Under  the  influence  of  the  osteo- 
blasts a  thin  layer  of  calcium  salts  is  deposited  between  the  osteoblasts  and  the 
calcified  fibers.  In  this  way  the  first  true  bone  is  formed,  and  the  calcification 
center  becomes  an  ossification  center.  Successive  layers  or  lamellae  of  calcium 
salts  are  laid  down  and  some  of  the  osteoblasts  become  enclosed  between  the 
lamellae  to  form  the  bone  cells  (Figs.  151  and  152).  The  spaces  in  which  the  bone 
cells  lie  are  the  lacuna.  At  the  same  time  the  fibers  also  are  enclosed  within  the 
bone  and  give  it  its  characteristic  fibrous  structure  (Fig.  152). 

Such  a  process  results  in  the  formation  of  irregular,  anastomosing  trabeculae 
of  bone.     The  spaces  among  the  trabeculae  are  known  as  primary  marrow 

Osteogenetis 

tissue  Osteoclast  Lacunae 


Bone 


— _  ,— -— ~-J 

Calcified  fibers  Osteoblasts 

FIG.  152. — From  vertical  section  through  parietal  bone  of  human  foetus  of  4  months. 
Bone  cells  not  shown  in  lacunae.     (Intramembranous  ossification.) 

spaces  and  contain  osteogenetic  tissue  (Fig.  151).  This  type  of  bone,  consisting 
of  irregular,  anastomosing  trabeculae  and  enclosed  marrow  spaces,  is  known  as 
spongy  bone.  The  spongy  bone  thus  formed  is  covered  on  its  outer  side  by  a 
layer  of  connective  tissue  which  from  its  position  is  called  the  periosteum 
(Fig.  151),  and  which  represents  a  part  of  the  original  embryonic  connective 
tissue  membrane  in  which  the  bone  was  laid  down.  During  its  development 
the  periosteum  becomes  an  exceedingly  dense  fibrous  membrane  which  is  closely 
applied  to  the  surface  of  the  bone. 

In  a  growing  embryo,  provision  must  be  made  for  increase  in  the  size  of  the 
cranial  cavity  to  accommodate  the  growing  brain.  This  is  accomplished  in 
the  following  manner :  On  the  inner  surface  of  the  newly  formed  bone,  large 
multinuclear  cells  appear,  which  are  known  as  osteoclasts  (bone  destroyers). 
The  osteoclasts  are  unusually  large  cells  with  a  large  number  of  nuclei  and 
abundant  cytoplasm,  and  in  sections  can  be  seen  lying  in  depressions  in  the 


172 


TEXT-BOOK  OF  EMBRYOLOGY. 


bone — Howslip's  lacuna  (Fig.  152).  They  apparently  possess  the  power  of 
dissolving  bone  tissue.  While  the  destruction  of  bone  by  the  osteoclasts  is 
going  on  on  the  inner  surface,  new  bone  is  being  formed  on  the  outer  surface, 
especially  under  the  periosteum  where  the  osteoblasts  are  most  numerous. 
Thus  the  layer  of  bone  gradually  comes  to  lie  farther  and  farther  out  and  the 
cranial  cavity  is  enlarged.  So  long  as  the  cranial  cavity  continues  to  enlarge 


Cartilage 


Osteogenetic  tissue 

Intracartilaginous 
bone 

Subperiosteal 
bone 


Blood  vessels 


Periosteum 
(perichondrium) 


/•  Ossification  center 


Calcification  zone 


FIG.  153. — Longitudinal  section  of  one  of  the  metatarsal  bones  of  a  sheep  embryo. 
(Intracartilaginous  ossification.) 

the  new  bone  is  of  the  spongy  variety,  but  toward  the  end  of  development  the 
trabeculae  become  thicker  and  finally  come  together  to  form  the  compact  bone 
characteristic  of  the  roof  of  the  skull.  The  fact  that  the  new  bone  laid  down 
during  the  enlargement  of  the  cranial  cavity  is  laid  down  under  the  periosteum 
has  led  to  the  term  subperiosteal  ossification.  The  process  is  essentially  the 
same  as  in  the  original  intramembranous  ossification. 

INTRACARTILAGINOUS  OSSIFICATION. 

In  this  type  of  ossification  hyalin  cartilage  is  first  formed  in  a  shape  which 
corresponds  very  closely  to  the  shape  of  the  future  bone.  For  example,  the 
femur  is  first  represented  by  a  piece  of  hyalin  cartilage  which  develops  from 


THE   CONNECTIVE  TISSUES  AND   THE  SKELETAL  SYSTEM.  173 

the  original  embryonic  connective  tissue.  On  the  surface  of  the  cartilage  a 
membrane  of  dense  fibrous  connective  tissue,  known  as  the  perichondrium, 
develops  (Fig.  153).  In  most  cases,  ossification  begins  about  the  middle 
of  the  piece  of  cartilage,  corresponding  to  the  middle  of  the  shaft  of  a  long 
bone  (Fig.  153).  The  cell  spaces  enlarge  and  in  some  cases  the  septa  of  matrix 
between  the  enlarged  spaces  break  down,  so  that  several  cells  may  lie  in  one 
space.  The  cell  spaces  radiate  from  a  common  center,  but  a  little  later  they 
come  to  lie  in  rows  parallel  with  the  long  axis  of  the  mass  of  cartilage.  During 
these  early  changes  lime  salts  are  deposited  in  the  matrix  of  the  cartilage  in 
this  region,  and  the  portion  so  involved  is  known  as  a  calcification  center. 

So  far  the  process  is  preparatory  to  actual  bone  formation.     Then  small 
blood  vessels  from  the  perichondrium  (periosteum)  grow  into   the  cartilage, 

Periosteal  bud 

Cartilage 
cell  spaces  ^~~^r^  ^-^         ^    Cartilage  cells 


*  /^  Hk    ^  Cartilage  matrix 

t^«&3I^^^;^^£Si~3feE^=a^»iSF. 


Periosteum 
(Perichondrium) 


FIG.  154. — From  section  of  one  of  the  tarsal  bones  of  a  pig  embryo      Showing  periosteal  bud 
pushing  into  the  cartilage  at  the  ossification  center.     (Intracartilaginous  ossification.) 

carrying  with  them  some  of  the  embryonic  connective  tissue.  These  little 
ingrowths  of  connective  tissue  and  blood  vessels  are  known  as  periosteal  buds 
(Fig.  154).  The  septa  between  the  enlarged  cartilage  cell  spaces  break  down 
still  further,  forming  still  larger  spaces  into  which  the  periosteal  buds  grow. 
Many  of  the  connective  tissue  cells  are  transformed  into  osteoblasts — oval  or 
round  cells  with  distinct  nuclei  and  a  considerable  amount  of  cytoplasm — and 
with  the  fibers  and  blood  vessels  constitute  osteo genetic  tissue  (Fig.  155).  The 
cartilage  cells  in  this  region  disintegrate  and  disappear,  and  the  cavity  formed 
by  the  coalescence  of  the  cell  spaces  constitutes  the  primary  marrow  cavity  (Fig. 
155).  From  the  primary  marrow  cavity  osteogenetic  tissue  pushes  in  both 
directions  toward  the  ends  of  the  cartilage.  The  transverse  septa  between  the 
enlarged  cartilage  cell  spaces  break  down,  leaving  a  few  longitudinal  septa 
which  form  the  walls  of  long  anastomosing  channels  which  are  continuous  with 


174  TEXT-BOOK  OF  EMBRYOLOGY. 

the  primary  marrow  cavity.  The  osteoblasts  arrange  themselves  in  rows  along 
the  septa  of  calcined  cartilage  and  a  thin  layer  or  lamella  of  calcium  salts  is 
deposited  between  them  and  the  cartilage.  Successive  lamellae  are  deposited 
in  the  same  manner  and  some  of  the  osteoblasts  become  enclosed  to  form  bone 
cells  (Fig.  156).  The  cartilage  in  the  center  gradually  disappears.  This 
region  where  bone  formation  is  going  on  is  known  as  an  ossification  center  (Fig. 
153)  and  the  irregular  anastomosing  trabeculae  of  bone  with  the  enclosed  marrow 
spaces  constitute  primary  spongy  bone. 

From  this  time  on,  ossification  gradually  progresses  toward  each  end  of  the 
cartilage,  and  at  the  same  time  a  special  modification  of  the  cartilage  precedes 
it.  Nearest  the  ossification  center  the  cartilage  cell  spaces  become  enlarged  and 

Cartilage  cell  spaces 
(primary  marrow  space) 


Disintegrating 
cartilage  cells 


Cartilage  cell 
spaces 


Blood  vessel 


m Trabecula 

of  cartilage 


L 


Osteogenetic  tissue  in 
primary  marrow  space 


FIG.  155.- — From  same  section  as  Fig.  153;  showing  osteogenetic  tissue  pushing  into  the  cartilage 
and  breaking  it  up  into  trabeculae.     (Intracartilaginous  ossification.) 

arranged  in  rows  and  contain  cartilage  cells  in  various  stages  of  disintegration. 
Some  of  the  septa  break  down,  leaving  larger,  irregular  spaces;  the  remaining 
septa  become  calcified  (Fig.  153).  Passing  away  from  the  center  of  ossifica- 
tion, there  is  less  enlargement  of  the  cell  spaces  and  they  have  a  tendency  to  be 
arranged  in  rows  transverse  to  the  long  axis  of  the  cartilage;  there  is  also  a  lesser 
degree  of  calcification.  The  region  of  modified  cartilage  at  each  end  of  the 
ossification  center  passes  over  gradually  into  ordinary  hyalin  cartilage  and  is 
known  as  the  calcification  zone.  It  always  precedes  the  formation  of  bone  as 
the  latter  process  moves  toward  the  end  of  the  cartilage  (Fig.  153). 

Along  with  the  type  of  ossification  just  described  subperiosteal  ossification 
also  occurs  (Fig.  153).  Beneath  the  periosteum  (perichondrium)  is  a  layer  of 
connective  tissue  the  cells  of  which  are  transformed  into  osteoblasts.  Thev 


THE   CONNECTIVE  TISSUES  AND   THE   SKELETAL  SYSTEM. 


175 


deposit  layers  of  calcium  salts  on  the  surface  of  the  cartilage  in  the  same 
manner  as  around  the  trabeculae  inside  the  cartilage. 

The  transformation  of  the  spongy  bone  into  compact  bone  is  peculiar 
in  that  the  former  is  dissolved  and  then  replaced  by  new  bone.  This 
dissolution  is  brought  about  by  the  action  of  the  osteoclasts — large  mul- 
tinuclear  cells  the  origin  of  which  is  not  known.  By  the  process  of  dis- 
solution the  marrow  spaces  are  increased  in  size  and  are  known  as  Haver- 
sian  spaces.  Within  these  spaces  new  bone  is  then  deposited  layer  upon  layer, 
under  the  influence  of  the  osteoblasts,  until  the  Haversian  spaces  are  reduced 
to  narrow  channels,  the  Haversian  canals.  The  layers  of  bone  are  the  Haver- 
sian lamella.  The  interstitial  lamella  in  compact  bone  have  two  possible 
origins.  They  may  be  the  remnants  of  certain  lamellae  of  the  original  spongy 


Blood  vessel 


Bone 


Cartilage 


Bone  cell 


Cartilage  cell 


Cartilage  cell  space 


FIG.  156. — From  same  section  as  Fig.  153;  showing  bone  deposited  around  one  of  the 
trabeculae  of  cartilage.     (Intracartilaginous  ossification.) 

bone  which  were  not  removed  in  the  enlargement  of  the  primary  marrow  spaces, 
or  they  may  be  parts  of  early  formed  Haversian  lamellae  which  were  later  more 
or  less  replaced  by  other  Haversian  lamellae. 

The  fact  should  be  emphasized  that  although  it  is  convenient  to  describe 
three  types  of  bone  formation,  the  three  do  not  differ  essentially  from  one 
another.  The  similarity  of  intramembranous  and  subperiosteal  ossification  has 
already  been  noted  (p.  172).  In  both  these  types  the  bone  is  developed  within 
a  membrane  of  embryonic  connective  tissue  by  a  transformation  of  this  tissue 
into  osteogenetic  tissue  and  then  of  the  latter  into  bone.  The  only  way  in 
which  intracartilaginous  bone  formation  differs  from  the  other  two  types  is 
that  cartilage  is  first  formed  within  the  membrane  in  the  same  general  shape  as 
the  future  bone.  But  it  must  be  remembered  that  it  is  only  in  this  cartilage  that 
bone  is  developed  and  not  from  it,  the  bone  being  produced  by  osteogenetic 


176  TEXT-BOOK  OF  EMBRYOLOGY. 

tissue  which  in  turn  is  derived  from  the  embryonic  connective  tissue  brought 
into  the  cartilage  by  the  periosteal  bud. 

GROWTH  OF  BONES. — The  way  in  which  the  cranial  cavity  enlarges  has  been 
described  on  page  171.  While  the  process  of  enlargement  is  going  on,  the 
individual  bones  increase  in  size  principally  by  the  addition  of  new  bone  along 
their  edges. 

Intracartilaginous  bones  grow  both  in  diameter  and  in  length.  It  has 
already  been  stated  that  the  primary  spongy  bone  formed  in  cartilage  is  dis- 
solved and  that  new  bone  is  deposited  under  the  periosteum.  This  naturally 
brings  about  an  enlargement  of  the  primary  marrow  cavity  and  at  the  same 
time  an  increase  in  the  diameter  of  the  bone  as  a  whole.  From  this  it  is  obvious 
that  the  compact  bone  of  the  shaft  of  a  long  bone  is  of  subperiosteal  origin,  the 
intracartilaginous  bone  having  been  completely  absorbed. 


A.  B 

FIG.  157. — Diagram  representing  growth  in  diameter  of  a  long  bone. 

from  Flourens. 

The  fact  that  the  osseous  tissue  bordering  the  marrow  cavity  is  absorbed  and  that  new 
bone  is  deposited  under  the  periosteum  can  be  quite  clearly  demonstrated.  A  young 
growing  animal  is  fed  for  a  few  weeks  on  madder,  which  colors  all  the  bone  formed  during  that 
time  a  distinct  red.  If  the  animal  is  then  killed  and  sections  made  of  the  long  bones,  the 
outer  part  of  the  latter  will  appear  a  distinct  red.  Another  growing  animal  is  fed  on  madder 
for  a  few  weeks,  then  allowed  to  live  a  few  weeks  longer  without  madder.  Then  if  it  is 
killed  and  sections  made  of  the  bones,  the  red  bone  is  found  to  be  covered  with  a  layer  of 
uncolored  bone  which  was  deposited  after  the  madder  feeding  had  been  stopped.  If  a 
young  growing  animal  is  fed  on  madder  for  a  time  and  then  allowed  to  live  long  enough 
without  madder,  the  red  bone  will  be  found  lining  the  marrow  cavity.  (See  Fig.  157.) 

Growth  in  length  of  the  long  bones  takes  place  in  a  different  manner.  The 
primary  center  of  ossification  is  situated  near  the  middle  of  the  piece  of  cartilage, 
and  ossification  proceeds  in  both  directions  toward  the  ends  of  the  cartilage  to 
produce  the  diaphysis  or  shaft  of  the  bone.  In  each  end  of  the  cartilage  there 
appears  a  secondary  center  from  which  ossification  proceeds  in  all  directions  to 
produce  the  epiphysis.  Between  the  shaft  and  epiphysis  a  disk  of  cartilage 
remains,  and  here,  so  long  as  the  bone  is  growing,  new  cartilage  continues  to  be 
formed.  At  the  same  time  new  bone  is  being  formed  in  the  new  cartilage, 


THE   CONNECTIVE  TISSUES  AND  THE  SKELETAL   SYSTEM. 


177 


principally  in  the  part  next  the  shaft.  This  produces  an  elongation  of  the 
shaft,  the  two  epiphyses  being  carried  farther  and  farther  apart,  and  conse- 
quently a  lengthening  of  the  bone  as  a  whole.  When  the  bone  reaches  the 
required  length,  the  cartilage  disk  diminishes  and  finally  is  wholly  replaced  by 
bone,  being  represented  in  the  adult  only  by  the  epiphyseal  line.  (See  Fig.  158.) 
MARROW. — The  forerunner  of  marrow  is  the  osteogenetic  tissue  in  the  pri- 
mary marrow  spaces,  which  in  turn  is  derived  from  embryonic  connective  tissue 
(Fig.  155).  During  the  development  of  bone,  great  numbers  of  osteoblasts  are 


FIG.  158. — Longitudinal  section  from  head  of  femur  of  young  dog.  Photograph. 
The  head  of  the  femur  is  shown  in  the  upper  part  of  the  figure,  the  end  of  the  shaft  in  the  lower 
part.  Between  the  two  the  lighter  line  represents  the  cartilage  between  the  primary  center 
of  ossification  (shaft)  and  the  secondary  center  (epiphysis,  head),  and  marks  the  site  of  the 
epiphyseal  line.  The  lighter  portion  covering  the  head  represents  the  cartilage  bordering 
the  joint  cavity. 


constantly  being  differentiated  from  the  connective  tissue  cells  and  many  of 
these  ultimately  become  bone  cells.  When  development  ceases,  osteoblasts 
cease  to  become  differentiated.  When  dissolution  of  bone  becomes  neces- 
sary, osteoclasts  appear.  Their  origin  is  not  known  with  certainty.  One 
view  is  that  they  represent  several  osteoblasts  which  have  fused  to  form  a 
single,  large  multinucleated  cell.  Their  relation  to  the  myeloplaxes  (giant 
cells)  in  adult  marrow  is  also  a  matter  of  doubt,  though  it  is  possible  that 
the  polykaryocytes  are  their  direct  descendants.  The  myeloUasts,  or  pro- 
genitors of  the  myelocytes,  are  approximately  spherical  cells,  larger  than  white 


178 


TEXT-BOOK  OF  EMBRYOLOGY. 


blood  cells,  mononuclear  and  with  slightly  basophilic  cytoplasm.  They 
probably  arise  from  mesenchymal  cells  or  even  from  the  elements  of  the 
reticular  tissue,  and  probably  also  constitute  the  cells  from  which  not  only 
the  myelocytes  but  also  red  and  white  blood  cells  are  derived.  In  forming 
the  myelocyte  series  they  acquire  certain  granules  in  the  cytoplasm  which 
may  be  neutrophile,  acidophile  or  basophile,  giving  the  cell  its  distinguish- 
ing character.  The  bone  marrow  in  the  adult  is  normally  the  only  source 
of  erythrocytes  and  one  of  the  sources  of  leucocytes.  Further  discussion 
of  these  cells  will  be  found  on  page  271.  In  young  marrow  there  is  little 
or  no  fat  present,  but  in  later  life  many  of  the  connective  tissue  cells  are 
transformed  into  fat  cells  (p.i68),so  that  these  form  the  greater  part  of 
the  marrow.  Such  a  process  occurs  most  extensively  in  the  shaft  of  the  long 
bones  and  gives  rise  to  " yellow"  marrow.  In  the  heads  of  the  long  bones, 
in  the  ribs,  and  in  the  short  bones  the  marrow  retains  its  earlier  character 
and  is  known  as  "red"  marrow. 

THE  DEVELOPMENT  OF  THE  SKELETAL  SYSTEM. 
The  Axial  Skeleton. 

The  Notochord. — The  notochord  (chorda  dorsalis)  constitutes  the 
primitive  axial  skeleton  of  all  Vertebrates,  yet  it  differs  from  the  other  skeletal 
elements  in  that  it  is  a  derivative  of  the  entoderm.  In  man  it  is  merely  a  tran- 
sient structure  and  disappears  early  in  foetal  life,  leaving  but  a  slight  trace  of 
itself  in  the  intervertebral  disks.  In  embryos  of  2-3  mm.  the  cells  of  the 


Mesoderm"" — 


Anlage  of 
notochord — 


Entoderm 


FIG.  159. — From  transverse  section  of  human  embryo  with  8  pairs  of 
primitive  segments  (2.69  mm.).     Kollmann. 

entoderm  just  ventral  to  the  neural  groove  become  slightly  differentiated 
(Fig.  159)  and  then  form  a  groove  with  a  ventral  concavity.  The  groove  closes 
in,  becomes  constricted  from  the  parent  tissue  (entoderm)  and  lies  just  ventral  to 
the  neural  tube,  where  it  soon  becomes  surrounded  by  mesodermal  tissue.  This 
structure  is  the  notochord  and  constitutes  a  solid,  cylindrical  cord  of  cells 
extending  from  a  point  just  caudal  to  the  hypophysis  to  the  caudal  extremity  of 
the  embryonic  body.  In  embryos  of  17-20  mm.  the  mesodermal  tissue  around 
the  notochord  becomes  modified  to  form  the  chordal  sheath.  On  account  of  its 
position  the  notochord  naturally  becomes  embedded  in  the  developing  vertebral 


THE  CONNECTIVE  TISSUES  AND  THE   SKELETAL  SYSTEM.  179 

column,  extending  through  the  bodies  of  the  vertebrae  and  the  intervertebral 
disks.  The  cells  are  at  first  of  an  epithelial  nature  (Fig.  159),  but  those  within 
the  vertebral  bodies  become  vacuolated  and  broken  up  into  irregular,  multinu- 
clear  masses  which  then  disappear.  The  cord  is  thus  first  interrupted  in  the 
vertebrae,  leaving  only  the  segments  within  the  intervertebral  disks.  Later  these 
segments  also  undergo  degenerative  changes,  but  persist  as  the  so-called  pulpy 
nuclei. 

While  the  notochord  is  morphologically  the  forerunner  of  the  axial  skeleton, 
and  persists  as  a  whole  in  Amphioxus,  and  in  part  in  Fishes  and  Amphibia,  in 
the  higher  forms  it  is  almost  exclusively  an  embryonic  structure  with  little  or  no 
functional  significance.  It  differs  in  origin  from  the  true  skeletal  elements  and 
becomes  involved  with  them  only  to  disappear  as  they  develop. 


Intersegmental 

artery 

Notochord 


i 


Parts  of  two 
adjacent  sclerotomes 


FIG.  160. — Five  myotomes  and  sclerotomes  from  sagittal  section  of  human  embryo  of  5  mm.  Bardeen. 

Each  sclerotome  is  differentiated  into  a  looser  cephalic  part  and  a  denser  caudal  part,  the  two 

being  separated  by  a  cleft  (fissure  of  von  Ebner). 

The  Vertebrae. — The  changes  which  occur  in  the  ventro-medial  parts  of  the 
primitive  segments  to  form  the  sclerotomes  have  already  been  described.  At 
the  same  time  it  wras  stated  that  the  vertebrae,  with  the  other  types  of  connective 
tissue  around  them,  were  derived  from  the  mesenchymal  tissue  of  the  sclerotomes 
(p.  163;  see  also  Fig.  142).  The  segmentally  arranged  masses  forming  the 
sclerotomes  are  separated  by  looser  tissue  in  which  the  intersegmental  arteries 
develop.  The  arteries  mark  the  boundaries  between  the  sclerotomes  (Fig.  160). 
About  the  third  week  of  development  the  caudal  part  of  each  sclerotome  con- 
denses to  form  a  more  compact  mass  of  tissue,  and  a  little  later  becomes 
separated  from  the  cephalic  part  by  a  small  cleft  (Fig.  161).  From  the  denser 
caudal  part  a  secondary  mass  of  tissue  grows  medially  and  meets  and  fuses  with 
its  fellow  of  the  opposite  side,  thus  enclosing  the  notochord.  The  medial  mass 


180 


TEXT-BOOK  OF  EMBRYOLOGY. 


thus  formed  may  be  considered  as  the  anlage  of  the  body  of  a  vertebra.  Another 
secondary  mass  also  grows  dorsally  between  the  myotome  and  the  spinal  cord, 
forming  the  anlage  of  the  vertebral  arch.  A  third  mass  grows  ventro-laterally  to 
form  the  costal  process  (Figs.  162  and  163).  The  looser  tissue  of  the  cephalic 
part  of  each  sclerotome  also  sends  an  extension  medially  to  surround  the 
notochord,  and  fills  up  the  intervals  between  the  succeeding  denser  (caudal) 
parts.  The  looser  part  also  forms  a  sort  of  membrane  between  the  succeeding 
vertebral  arches.  The  tissue  between  the  denser  caudal  part  and  the  looser 
cephalic  part  of  each  sclerotome  is  destined  to  give  rise  to  an  intervertebral 
Jibrocartilage.  While  the  denser  tissue  forming  the  caudal  part  of  each  sclero- 


Dermis 


Myotome 


Notochord 

Cleft 

Intersegmental  artery 

Perichordal  sheath 
Intervertebral  disk 
Interdiscal  membrane 


FIG.  161. — Six  myotomes  and  sclerotomes  from  sagittal  section  of  human  embryo  of  6  mm. 
Bardeen.     Compare  with  Fig.  160. 

tome  probably  gives  rise  to  the  greater  part  of  a  vertebra,  the  looser  tissue  of  the 
cephalic  part  is  also  involved  in  the  formation  of  the  cartilaginous  body,  as  will 
be  noted  again  in  the  following  paragraph.  The  peculiar  feature  of  the  process 
is  that  the  denser  caudal  part  of  a  sclerotome  becomes  associated  with  the  looser 
cephalic  part  of  the  next  succeeding  sclerotome,  so  that  each  vertebra  is  derived 
from  parts  of  two  adjacent  sclerotomes  and  not  from  a  single  sclerotome.  This 
naturally  brings  about  an  alternation  of  vertebra  and  myotomes  (Fig.  161). 

So  far  the  anlagen  of  the  vertebrae  are  in  the  so-called  blastemal  stage. 

Following  the  blastemal  stage  and  beginning  in  human  embryos  of  about  15 
mm.,  comes  the  cartilaginous  stage  in  which  the  mesenchymal  anlagen  of  the 
vertebras  are  converted  into  embryonic  hyalin  cartilage.  In  the  body  of  each 
vertebra  a  center  of  chondrification  appears  in  the  looser  tissue  of  the  caudal 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


181 


part  and  gradually  enlarges  and  involves  the  denser  cephalic  part.  It  is  to  be 
noted  that  the  denser  tissue  of  the  cephalic  part  of  a  vertebral  body  corresponds 
to  the  caudal  part  of  a  sclerotome.  Two  chondrification  centers  appear,  one  on 


Costal  process 


Aorta 


Stomach 


Arch  of 
vertebra 


Notochord 


Body  of 
vertebra 


Mesonephros 


Liver 


FIG.  162. — Transverse  section  (dorsal  part)  of  pig  embryo  of  14  mm.     Photograph. 

each  side  of  the  medial  line,  but  the  two  soon  fuse  around  the  notochord  to 
form  a  single  center.  In  addition  to  the  center  in  the  body  of  the  vertebra,  one 
also  appears  in  each  half  of  the  vertebral  arch,  and  one  in  each  costal  process 


Interdorsal  membrane 


Notochord 


Bodies  of 
vertebrae 


Costal  process 
FIG.  163. — Models  of  three  vertebrae  in  the  blastemal  stage;  from  an  embryo  of  n  mm.     Bardeen. 

(Fig.  164).  All  these  centers  then  enlarge  and  unite  to  form  a  single  mass  of 
cartilage  which  corresponds  quite  accurately  in  shape  to  the  future  bony 
vertebra.  Processes  then  grow  out  from  the  vertebral  arch.  These  represent 


182 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  transverse  and  articular  processes  (Fig.  165).  Each  half  of  a  vertebral 
arch  meets  its  fellow  of  the  opposite  side  dorsal  to  the  spinal  cord,  and  from 
the  point  of  meeting  the  spinous  process  grows  out.  The  costal  processes  do 


Costal  process 
(rib) 


Body  of 
vertebra 


Costal  process 
(rib) 


Aorta 


Pleural  cavity  Liver  (Esophagus  Lung 

FIG.  164. — Transverse  section  (dorsal  part)  of  pig  embryo  of  35  mm.     Photograph. 

not  retain  their  connection  with  the  body  of  the  vertebra,  but  break  away 
and  become  the  rib  cartilages,  as  will  be  noted  again  in  connection  with  the 
development  of  the  ribs. 

Following  the  cartilaginous  stage  is  the  stage  of  ossification  in  which  the 

Arch  of  vertebra 
Post,  articular 
process 

Transverse  process 


Anterior  articular  process 

FIG.  165. — Models  of  the  6th,  7th  and  8th  thoracic  vertebrae  of  an  embryo  of  33  mm. 

(dorsal  view).     Bardeen. 
On  the  right  the  cartilage  is  shown,  on  the  left  the  surrounding  fibrous  tissue. 

vertebrae  become  ossified  and  acquire  the  adult  condition.  Ossification  begins 
during  the  third  month  of  fcetal  life  and  extends  over  a  long  period,  even  up  to 
the  age  of  twenty-five  years.  A  single  center  of  ossification  appears  in  the  body 


THE   CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


183 


of  each  vertebra,  and  following  this  a  center  in  each  half  of  the  vertebral  arch 
(Fig.  1 66).  Osseous  tissue  then  gradually  replaces  the  cartilage.  The  two 
halves  of  an  arch  fuse  dorsal  to  the  spinal  cord  during  the  first  year  of  post- 
natal life,  thus  completing  the  bony  arch.  The  arch  fuses  with  the  body  of  the 


Med.  ossif.  cents 

FIG.  166. — Thoracic  vertebra  and  ribs  of  human  embryo  of  55  mm.  (middle  of 

3rd  month).     Kollmann's  A  tlas. 
Cartilage  indicated  by  stippled  areas,  ossification  centers  by  irregular  black  lines. 

vertebra  between  the  third  and  eighth  years.  Thus  it  is  seen  that  the  process  of 
ossification  is  a  slow  one,  and  this  is  even  more  striking  when  one  considers  the 
formation  of  the  secondary  centers.  For  at  about  the  age  of  puberty  a  secondary 
center  appears  in  each  of  the  cartilages  that  cover  the  ends  of  the  vertebrae,  pro- 

Spinous  process 
Transverse  process 
Articular  process 


Body  of  vertebra 


Upper  epiphyseal 
plate 


FIG.  167. — Lumbar  vertebra  (lateral  view)  showing  secondary  centers  of  ossification.     Sappey. 

ducing  disks  of  bone— the  epiphyses.  A  secondary  center  also  appears  in  the 
cartilage  on  the  tip  of  each  spinous  process  and  transverse  process,  and  in  the 
lumbar  vertebrae  one  appears  also  on  the  tip  of  each  articular  process  (Fig.  167). 
The  epiphyses  unite  with  the  vertebrae  any  time  between  sixteen  and  twenty- 


184 


TEXT-BOOK  OF  EMBRYOLOGY. 


five  years.  About  the  twenty-fifth  year  the  sacral  vertebrae  unite  to  form  a 
single  mass  of  bone,  and  a  similar  union  also  takes  place  between  the  more  or 
less  rudimentary  coccygeal  vertebrae. 

While  the  general  plan  of  development  is  practically  the  same  in  all  the 
vertebrae,  there  are  a  few  noteworthy  modifications.  The  greatest  modification 
is  in  the  atlas  and  epistropheus  (axis).  The  entire  atlas  is  formed  from  the 
denser  caudal  part  of  a  sclerotome.  The  lateral  mass  and  the  posterior  (dorsal) 
arch  represent  the  vertebral  arch.  The  anterior  (ventral)  arch  represents  the 
hypochordal  bar,  a  plate  of  cartilage  which  develops  in  all  vertebrae  ventral  to 
the  notochord  but  disappears  in  all  except  the  atlas.  A  body  also  develops 
but  instead  of  forming  part  of  the  atlas  it  unites  with  the  body  of  the  epistro- 
pheus to  form  the  dens  (odontoid  process)  of  the  latter. 


Clavicle 


Suprasternal  cartilage 


Sternal  bar 


7th  rib 


FIG.  168. — Ventral  view  of  developing  sternum  of  human  embryo  of  30  mm. 
(beginning  of  3rd  month).     Ruge,  Kollmann's  Atlas. 

The  various  ligaments  of  the  vertebral  column  are  derived  from  the  embry- 
onic connective  tissue  surrounding  the  vertebrae.  The  embryonic  connective 
tissue  in  the  clefts  separating  the  developing  vertebrae  is  transformed  into  the 
intervertebral  fibrocartilages. 

The  Ribs. — It  has  been  stated  in  a  previous  paragraph  that  the  costal  proc- 
esses arise  as  outgrowths  from  the  denser  caudal  parts  of  the  sclero tomes;  that 
they  grow  in  a  ventro-lateral  direction  and  consequently  are  at  first  connected 
with  and  are  parts  of  the  bodies  of  the  vertebrae  (Figs.  162  and  165).  These 
costal  processes  are  the  anlagen  of  the  ribs,  and  they  continue  to  grow  ventrally 
until  they  practically  encircle  the  body,  the  ventral  ends  of  a  number  of  them 
fusing  in  the  medial  line  to  form  the  sternum.  The  primary  junctions  between 
the  costal  processes  and  vertebrae  are  dissolved,  and  the  embryonic  connective 
tissue  in  this  region  gives  rise  to  the  costo-vertebral  ligaments.  The  dissolu- 
tion of  the  junctions  leaves  the  ribs  simply  articulating  with  the  vertebrae. 


THE   CONNECTIVE  TISSUES  AND   THE  SKELETAL  SYSTEM. 


185 


A  chondrification  center  appears  in  each  costal  process,  shortly  after  that  in 
the  body  of  the  vertebra,  and  from  this  point  the  formation  of  cartilage 
gradually  extends  throughout  the  entire  rib. 

Ossification  begins  during  the  third  month  at  a  center  which  is  situated  near 
the  angle  of  the  rib  (Fig.  166).  At  the  age  of  eight  to  fourteen  years  a  second- 
ary center  appears  in  each  capitulum  and  tuber culum  and  subsequently  fuses 
with  the  rest  of  the  rib  at  the  age  of  fourteen  to  twenty-five  years.  As  the 
tuberculum  develops,  the  transverse  process  of  the  corresponding  vertebra 
grows  ventrally  and  caudally  to  meet  it  and  form  the  articulation. 

The  ribs  reach  the  highest  degree  of  development  in  the  thoracic  region 
where  one  develops  on  each  side,  corresponding  to  each  vertebra.  The  first 
seven  or  eight  thoracic  ribs  extend  almost  to  the  mid- 
ventral  line  and  are  attached  to  the  sternum;  the  last  four 
or  five  become  successively  shorter  and  are  only  indirectly 
or  not  at  all  attached  to  the  sternum.  In  the  cervical 
region  the  ribs  do  not  reach  a  high  degree  of  development. 
Their  tips  simply  fuse  with  the  transverse  processes  of  the 
vertebras  and  their  heads  with  the  bodies  of  the  vertebrae, 
leaving  a  space — the  foramen  transversarium — through 
which  the  vertebral  vessels  pass.  The  seventh  cervical  rib 
may,  however,  reach  a  fairly  high  degree  of  development. 
In  the  lumbar  region  also  the  ribs  are  reduced  to  small 
pieces  of  bone  which  are  firmly  united  with  the  transverse 
processes  and  form  the  accessory  processes.  In  the  sacral 
region  the  rudimentary  ribs  unite  to  form  the  lateral  part 
(pars  lateralis)  of  the  sacral  bone.  After  the  blastemal 
stage  there  are  no  indications  of  ribs  in  the  coccygeal  region. 
In  the  blastemal  stage,  however,  there  is  a  small  bit  of  tissue  FIG.  169.— Sternum  of 
which  probably  represents  the  anlage  of  a  rib,  but  soon 
fuses  with  the  transverse  process. 

The  Sternum. — The  sternum  is  formed  by  the  fusion 
of  the  ventral  ends  of  the  first  eight  or  nine  thoracic  ribs. 
A  longitudinal  bar  is  first  formed  on  each  side  of  the  medial 
line  by  the  fusion  of  the  ventral  ends  of  the  ribs  on  each  side;  then  the  two  bars 
unite  in  the  medial  line  to  form  a  single  piece  of  cartilage  (Figs.  168  and  169). 
Subsequently  the  last  one  or  two  ribs  become  separated  from  the  sternum, 
leaving  only  seven  or  eight  connected  with  it.  At  the  cephalic  end  of  the 
sternum  two  separate  pieces  of  cartilage — episternal  cartilages — appear,  with 
which  the  clavicles  articulate  (Fig.  168).  These  usually  unite  with  the  longi- 
tudinal bar  to  form  a  part  of  the  manubrium,  but  they  may  remain  separate 
and  ossify  to  form  the  supr asternal  bones  (ossa  suprasternalia). 


old  child, 
centers  of 
ossification.  Seven 
ribs  are  attached  on 
the  right  side,  8  on 
the  left.  Markcnvski, 
Kollmann's  Atlas. 


186 


TEXT-BOOK  OF  EMBRYOLOGY. 


Ossification  begins  in  the  sternum  about  the  end  of  the  fifth  month  of  foetal 
life.  In  each  of  the  two  cephalic  segments  a  single  center  appears;  caudal  to  the 
second  segment  a  series  of  paired  centers  appears,  and  later  the  centers  of  each 
pair  fuse  into  a  single  center  (Fig.  169).  The  paired  centers  possibly  represent 
epiphyses  of  the  ribs.  Sometimes,  however,  the  centers  appear  as  a  single 
series,  that  is,  with  no  indication  of  a  paired  character.  The  ossification 
of  the  most  cephalic  segment,  along  with  the  episternal  cartilages,  produces  the 
manubrium  sterni.  Ossification  of  the  following  six  or  seven  segments  and  their 
union  produce  the  corpus  sterni.  The  bars  formed  from  the  most  caudal  ribs 
(excluding  the  false  ribs)  form  the  xyphoid  process.  This  process  remains  car- 


Olfactory  organ 
Hypophysis 
Visual  organ 

Prechordal  plate 

Auditory  organ 

Parachordal  plate 

Notochord 


Nasal  septum 

Olfactory  organ 
Hypophysis 
Visual  organ 

Prechordal  plate 
Auditory  organ 


Basal  (parachordal) 
plate 

Notochord 


FIG.  170.  FIG.  171. 

FIG.  170. — Diagram  of  first  stage  in  the  development  of  the  cartilaginous 

primordial  cranium.     Wiedersheim. 
FIG.  171. — Diagram  of  later  stage  of  same.     Wiedersheim. 

tilaginous  for  a  long  period,  and  may  be  single,  perforated,  or  bifurcated,  de- 
pending upon  the  degree  of  fusion  between  the  two  primary  bars. 

The  Head  Skeleton. — Topographically  the  skeleton  of  the  head  appears 
as  the  cephalic  part  of  the  axial  skeleton.  Structurally  it  is  decidedly  different, 
for  it  is  adapted  to  different  conditions.  The  neural  tube  here  becomes  differ- 
entiated into  the  brain  with  its  many  and  dissimilar  parts.  In  connection  with 
the  brain  the  complicated  sense  organs  (nose,  eye  and  ear)  arise.  A  part  of 
the  alimentary  tract  and  portions  of  the  visceral  arches  are  also  inclosed 
within  the  head.  The  head  skeleton  is  specially  modified  to  accommodate 
these  highly  developed  organs,  and  becomes  extremely  complicated.  In 
general  the  skeleton  in  any  part  of  the  body  adapts  itself  to  the  other  structures 
and  not  the  other  structures  to  the  skeleton. 

The  anlage  of  the  skull  is  a  mass  of  embryonic  connective  tissue  which  sur- 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


187 


rounds  the  cephalic  end  of  the  notochord,  extends  from  there  into  the  nasal 
region  and  also  extends  around  the  sides  and  dorsal  part  of  the  neural  tube 
(brain).  Unlike  the  anlage  of  the  vertebral  column,  the  anlage  of  the  skull 
shows  no  distinct  division  into  primitive  segments.  The  only  indications  of  a 
segmental  character  are  referred  to  in  a  succeeding  paragraph  (small  print, 
p.  189). 

The  next  step  in  the  development  of  the  skull  is  the  appearance  of  cartilage 
in  certain  regions  of  the  embryonic  connective  tissue.  On  account  of  the  com- 
plicated arrangement  of  the  cartilage  in  the  human  skull,  it  is  best  to  consider 


Palatoquadrate 

Palatoquadrate 
Meckel's  cartilage 


Palatoquadrate 
Hypophysis 


Nasal  fossa 
Preorbital  process 


Roof  of  skull 
Marginal  bar 


Prechordal  plate 
Prootic  incisure 
Jugular  foramen 

}  Foramina  (VII  Nerve) 


Notochord 
>Otic  (auditory)  capsule 

Synotic  tectum 


FIG.  172.  —  Primordial  cranium  of  Salmo  salar  (salmon)  embryo  of  25  mm.     Dorsal  view.     Gaupp. 
Compare  with  Fig.  171  and  note  further  elaboration  of  parts  surrounding  the  sense  organs. 


first  its  more  simple  arrangement  in  the  lower  Vertebrates.  In  these  there  ap- 
pear in  the  embryonic  connective  tissue  around  the  cephalic  end  of  the  notochord 
two  bilaterally  symmetrical  pieces  of  cartilage,  which  extend  as  far  as  the 
hypophysis.  Then  two  other  bilaterally  symmetrical  pieces  appear,  extending 
from  the  hypophysis  to  the  nasal  region.  Subsequently  all  these  pieces  fuse 
into  a  single  mass  which  extends  from  the  cephalic  end  of  the  vertebral  column 
to  the  tip  of  the  nose,  enclosing  the  end  of  the  notochord  and,  to  a  certain  ex- 
tent, the  ear,  eye  and  olfactory  apparatus.  There  is  left,  however,  an  opening 
for  the  hypophysis.  From  this  mass  of  cartilage,  chondrification  extends  into 
the  embryonic  connective  tissue  along  the  sides  and  roof  of  the  cranial 


188 


TEXT-BOOK  OF  EMBRYOLOGY. 


cavity,  so  that  the  brain  and  sense  organs  are  practically  enclosed.  To  this 
capsule  the  term  cartilaginous  primordial  cranium  has  been  applied.  (See 
Figs.  170,  171,  172.) 

In  the  higher  Vertebrates,  chondrification  is  limited  to  the  basal  region  of  the 
skull,  while  the  side  walls  and  roof  are  formed  later  by  intramembranous  bone. 


Meckel's  cartilage 
Malleus 

Incus 


Int.  acoustic  pore 
Jugular  foramen 

Subarcuate  fossa 


Ala  magna  (sphenoid) 
Optic  foramen 

Ala  parva  (sphenoid) 

Sella  turcica 
Dorsum  sellae 


Foramina 
(VII  Nerve) 

Auditory 
capsule 


Foramen 


Foramen  (XII  Nerve) 


Large  occipital  foramen  Occipital 

(foramen  magnum)        (synotic  tectum) 

FIG.  173. — Dorsal  view  of  primordial  cranium  of  human  embryo  of  80  mm. 

(3rd  month).     Gaupp.  Hertwig. 

The  membrane  bones  of  the  roof  of  the  skull  have  been  removed.     Through  the  large  occipital 
foramen  can  be  seen  the  first  three  cervical  vertebrae. 


In  the  human  embryo  chondrification  occurs  first  in  the  occipital  and  sphenoidal 
regions,  and  then  gradually  extends  into  the  nasal  (ethmoidal)  region.  A  little 
later  it  spreads  somewhat  dorsally  in  the  occipital  and  sphenoidal  regions  to  form 
part  of  the  squamous  portion  of  the  occipital  and  the  wings  of  the  sphenoid.  At 
the  same  time  cartilage  develops  in  the  embryonic  connective  tissue  surround- 


THE   CONNECTIVE  TISSUES  AND   THE  SKELETAL  SYSTEM. 


189 


ing  the  internal  ear  to  form  the  periotic  capsule  which  subsequently  unites  with 
the  occipital  and  sphenoidal  cartilages.  The  pieces  of  cartilage  thus  formed  con- 
stitute the  chondrocranium. 

In  connection  with  the  development  of  the  caudal  part  of  the  occipital  cartilage  there  is 
an  interesting  feature  which  is  at  least  indicative  of  a  segmental  character.  In  some  of  the 
lower  Mammals  there  are  four  fairly  distinct  condensations  of  embryonic  connective  tissue 
just  cranial  to  the  first  cervical  vertebra,  corresponding  to  the  first  cervical  nerve  and  the 
three  roots  of  the  hypoglossal.  These  condensations  bear  a  general  resemblance  to  the 
primitive  segments  and  indicate  the  existence  of  four  vertebrae  which  are  later  taken  up  into 
the  chondrocranium.  In  the  human  embryo  the  condensations  are  less  distinct,  but  the 
existence  of  a  first  cervical  and  a  three-rooted  hypoglossal  nerve  in  this  region  suggests  an 
original  segmental  character.  If  this  is  true,  then  the  base  of  the  human  skull  is  formed 
from  the  unsegmented  chondrocranium  plus  four  vertebrae  which  become  incorporated  in 
the  occipital  region. 


Optic  foramen 


Ala  magna  (sphenoid) 

Ala  parva  (sphenoid) 


Vomer 
Palate  bone 


Mandible 

Meckel's  cartilage 

Cricoid  cartilage 


\  Styloid  process 
Cochlear  fenestra 

Foramen  (XII  Nerve) 


Thyreoid  cartilage 


FIG.  174. — Lateral  view  of  primordial  cranium  of  human  embryo  of  80  mm. 

(3rd  month).     Gaupp,  Hert-wig. 

The  membrane  bones  of  the  roof  of  the  skull  have  been  removed.     Compare  with  FIG.  173. 
maxilla,  vomer,  palate,  and  mandible  are  membrane  bones. 


The 


In  addition  to  the  chondrocranium,  other  cartilaginous  elements  enter  into 
the  formation  of  the  skull,  all  of  which  are  derived  from  the  visceral  arches. 
Not  all  the  arches,  however,  produce  cartilage;  for  in  the  maxillary  process  of 
the  first  arch,  which  forms  the  upper  boundary  of  the  mouth,  cartilage  does  not 
appear,  and  the  bones  which  later  develop  in  it  are  of  the  membranous  type. 
The  mandibular  process  of  the  first  arch  produces  a  rod  of  cartilage — Meckel's 
cartilage.  This  gives  rise,  at  its  proximal  end,  to  a  part  of  the  auditory  ossicles, 
but  the  cartilage  in  the  jaw  proper  soon  wholly  or  almost  wholly  disappears. 
The  cartilage  of  the  second  arch  becomes  connected  with  the  skull  in  the  region 


190 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  the  periotic  capsule.     The   cartilages  of  the  other  three  arches  are  only 
indirectly  connected  with  the  skull  and  will  be  considered  later. 

Figs.  1 73  and  174  show  the  condition  of  the  chondrocranium  in  a  human 
embryo  of  80  mm.  (third  month) .  Although  at  first  glance  it  seems  exceedingly 
complicated,  a  careful  study  and  comparison  of  the  various  parts  will  aid  the 
student  in  his  comprehension  of  the  cartilaginous  foundation  upon  which  the 
skull  is  built. 

OSSIFICATION  OF  THE  CHONDROCRANIUM. 

In  the  human  foetus  ossification  begins  in  the  occipital  region  during  the 
third  month.  Four  centers  appear  which  correspond  to  the  four  parts  of  the 
adult  occipital  bone  (Fig.  175).  (i)  An  unpaired  center  situated  ventral  to  the 
foramen  magnum.  From  this  center  ossification  proceeds  in  all  directions  to 


Interparietal 
(of  lower  forms) 


Squamous  part 
'  (intramemb.) 


Squamous 
part 


Kerkringius'  bone 


Squamous  part 
(intracartilag.) 


•Lateral  part 


Basilar  part 


FIG.  175. — Occipital  bone  of  human  embryo  of  21.5  cm.     Kollmann's  Atlas. 


form  the  pars  basilaris  (basioccipital).  (2  and  3)  Two  lateral  centers,  one 
on  each  side.  From  these,  ossification  proceeds  to  produce  the  partes  laterales 
(exoccipital)  which  bear  the  condyles.  (4)  A  center  dorsal  to  the  foramen, 
magnum.  This  produces  the  pars  squamosa  (supraoccipital)  as  far  as  the  supe- 
rior nuchal  line.  Beyond  this  line  the  pars  squamosa  is  of  intramembranous 
origin.  (See  p.  192.)  At  birth  the  four  parts  are  still  separated  by  plates  of 
cartilage.  During  the  first  or  second  year  after  birth  the  partes  laterales 
unite  with  the  pars  squamosa,  and  about  the  seventh  year  the  pars  basilaris 
unites  with  the  rest  of  the  bone. 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM.  191 

In  the  sphenoidal  region  ossification  begins  at  a  number  of  centers  which, 
as  in  the  occipital  region,  correspond  generally  to  the  parts  of  the  adult  sphenoid 
bone  (Fig.  176).  (i  and  2)  About  the  ninth  week  an  ossification  center 
appears  on  each  side  in  the  cartilage  which  corresponds  to  the  ala  magna 
(alisphenoid).  (3  and  4)  About  the  twelfth  week  a  center  appears  on  each 
side  which  corresponds  to  the  ala  parva  (orbitosphenoid).  (5  and  6)  A 
short  time  after  this  a  center  appears  on  each  side  of  the  medial  line  in  the 
basal  part  of  the  cartilage,  and  the  two  centers  subsequently  fuse  to  produce  the 
corpus  (basisphenoid).  (7  and  8)  Lateral  to  each  basal  center,  another  center 
appears  which  represents  the  beginning  of  the  lingula.  (9  and  10)  Finally 
two  centers  appear  in  the  basal  part  of  the  cartilage,  in  front  of  the  other 
basal  centers,  and  then  fuse  to  form  the  presphenoid.  As  in  the  case  of  the  oc- 
cipital bone,  not  all  of  the  adult  sphenoid  is  of  intracartilaginous  origin;  for  the 

Ala  parva- 

Ala  magna 


Lingula 


corpus 
'  (basisphenoid) 

FIG.  176. — Sphenoid  bone  of  embryo  of  3^-4  months.     Sappey. 
The  parts  that  are  still  cartilaginous  are  represented  in  black. 

upper  anterior  angle  of  each  ala  magna  is  of  intramembranous  origin,  as  are  also 
the  medial  and  lateral  laminae  of  the  pterygoid  process.  The  pterygoid  hamulus, 
however,  is  formed  by  the  ossification  of  a  small  piece  of  cartilage  which  de- 
velops on  the  tip  of  the  medial  lamina.  The  fusion  of  these  various  parts  oc- 
curs at  different  times.  The  lateral  pterygoid  lamina  unites  with  the  alisphe- 
noid before  the  sixth  month  of  foetal  life;  about  the  sixth  month  the  lingula  fuses 
with  the  basisphenoid,  and  the  presphenoid  with  the  orbitosphenoid.  The 
alisphenoid  and  medial  pterygoid  lamina  fuse  with  the  rest  of  the  bone  during 
the  first  year  after  birth.  The  union  of  the  basisphenoid  and  basioccipital 
usually  occurs  when  the  growth  of  the  individual  ceases,  though  the  two  bones 
may  remain  separate  throughout  life. 

In  the  region  of  the  periotic  capsule,  several  centers  of  ossification  appear  in 
the  cartilage  during  the  fifth  month.  During  the  sixth  month  these  centers 
unite  to  form  a  single  center  which  then  gradually  increases  to  form  the  pars 
petrosa  and  pars  mastoidea  of  the  adult  temporal  bone.  The  mastoid  process  is 


192  TEXT-BOOK  OF  EMBRYOLOGY. 

formed  after  birth  by  an  evagination  from  the  pars  petrosa,  and  is  lined  by  an 
evaginated  portion  of  the  mucosa  of  the  middle  ear.  The  other  parts  of  the 
temporal  bone  are  of  intramembranous  origin,  except  the  styloid  process  which 
represents  the  proximal  end  of  the  second  branchial  arch. 

In  the  ethmoidal  region,  conditions  become  more  complicated  on  account  of 
the  peculiarities  of  the  nasal  cavities,  and  on  account  of  the  fact  that  the  cartilage 
is  never  entirely  replaced  by  bone,  and  that  "membrane"  bones  also  enter  into 
more  intimate  relations  with  the  "cartilage"  bones.  The  ethmoidal  cartilage 
at  first  consists  of  a  medial  mass,  which  extends  from  the  presphenoid  region  to 
the  end  of  the  nasal  process,  and  of  a  lateral  mass  on  each  side,  which  is  situated 
lateral  to  the  nasal  pit  (Fig.  1 74) .  Ossification  in  the  lateral  mass  on  each  side 
produces  the  ethmoidal  labyrinth  (lateral  mass  of  ethmoid).  It  is  perhaps  not 
quite  correct  to  say  that  ossification  produces  the  ethmoidal  labyrinth,  for  at 
first  there  is  only  a  mass  of  spongy  bone  with  no  indication  of  the  honey-combed 
structure  characteristic  of  the  adult.  The  latter  condition  is  produced  by  a 
certain  amount  of  dissolution  of  the  bone  and  the  growth  of  the  nasal  mucosa 
into  the  cavities  so  formed.  By  the  same  process  of  dissolution  and  ingrowth  of 
nasal  mucosa  the  superior,  middle  and  inferior  concha  (turbinated  bones)  are 
formed.  The  medial  mass  of  cartilage  begins  to  ossify  after  birth  and  then  only 
in  its  upper  (superior)  edge.  It  forms  the  lamina  perpendicularis  and  crista 
galli  and  extends  into  the  nose  as  the  nasal  septum.  The  lower  (inferior)  edge 
remains  as  cartilage  until  the  vomer,  which  is  a  membrane  bone  (p.  194), 
develops,  after  which  it  is  partly  dissolved.  The  lamina  cribrosa  (cribriform 
plate)  is  formed  by  bony  trabeculae  which  extend  across  between  the  medial 
mass  and  the  lateral  masses  and  surround  the  bundles  of  fibers  of  the  olfactory 
nerve. 

MEMBRANE  BONES  OF  THE  SKULL. 

Under  this  head  we  shall  consider  only  those  bones  which  develop  apart 
from  the  visceral  arches,  those  which  involve  the  arches  being  considered  later. 
It  has  been  seen  that  by  far  the  greater  parts  of  the  bones  forming  the  base  of  the 
skull  are  of  intracartilaginous  origin.  On  the  other  hand,  those  forming  the 
sides  and  roof  of  the  skull  are  largely  of  intramembranous  origin.  In  the  case 
of  the  occipital  bone,  two  centers  of  ossification  appear  in  the  membrane  dorsal 
to  the  supraoccipital,  and  the  bone  so  formed  begins  to  unite  with  the  supra- 
occipital  during  the  third  month  of  fcetal  life.  At  birth  the  union  is  usually 
complete,  though  for  a  time  an  open  suture  may  persist  on  each  side.  The  bone 
derived  from  the  two  centers  forms  that  part  of  the  occipital  squama  which  is 
situated  above  the  superior  nuchal  line;  the  part  below  the  line  is  of  intracarti- 
laginous origin  (p.  190).  The  adult  occipital  is  thus  a  composite  bone,  partly 
of  intramembranous,  partly  of  intracartilaginous  origin. 


THE   CONNECTIVE  TISSUES   AND   THE   SKELETAL  SYSTEM. 


193 


The  temporal  is  also  a  composite  bone,  the  petrous  and  mastoid  parts 
and  the  styloid  process  being  of  intracartilaginous  origin,  while  the  temporal 
squama  and  the  tympanic  part-  are  of  intramembranous  origin.  During  the 
eighth  week  of  foetal  life  a  center  of  ossification  appears  in  the  membrane  in  the 
temporal  region,  and  the  bone  formed  from  this  center  subsequently  unites 
with  the  petrous  part  and  becomes  the  temporal  squama.  Another  center  ap- 
pears in  the  membrane  to  the  outer  side  of  the  periotic  capsule  and  produces  a 
ring  of  bone  around  the  external  auditory  meatus,  which  fuses  with  the  petrous 


Parietal 


Occipital 

fontanelle 


Occipital  -7 


Mastoid   - 
fontanelle 


Occipital 

Petrous 

Occipital 

Tympanic 

Styloid  process 

Stylohyoid  lig. 

Hyoid  (greater  horn) 


Sphenoidal 
fontanelle 


Cricoid 


Zygoma  tic 
Maxilla 

Mandible 

Meckel's  cartilage 
Hyoid  (lesser  horn) 

Thyreoid 


FIG.  177. — Diagram  of  skull  of  new-born  child.     Combined  from  McMnrrich  and  Kollmann. 
White  areas  represent  bones  of  intramembranous  origin:  dotted  areas  represent  bones  (not  derived 
from    branchial  arches)  of  intracartilaginous  origin;    black  areas   represent  derivatives  of 
branchial  arches. 


part  and  forms  the  tympanic  part  of  the  adult  bone.  It  gives  attachment  at  its 
inner  border  to  the  tympanic  membrane.  While  the  union  of  the  different 
parts  begins  during  foetal  life,  it  is  usually  completed  after  birth. 

The  sphenoid  bone  is  also  composed  of  parts  which  have  different 
origins.  The  body,  small  wings  and  large  wings  are  of  intracartilaginous 
origin,  the  pterygoid  process  of  intramembranous  origin.  About  the  eighth 
week  of  development  a  center  of  ossification  appears  in  the  mesenchyme  in  the 
lateral  wall  of  the  posterior  part  of  the  nasal  cavity  and  gives  rise  to  the  medial 
pterygoid  lamina.  On  the  tip  of  the  latter  a  small  piece  of  cartilage  appears  in 


194  TEXT-BOOK  OF  EMBRYOLOGY. 

which  ossification  later  takes  place  to  form  the  pterygoid  hamulus  (p.  191). 
The  lateral  pterygoid  lamina  is  also  of  intramembranous  origin  and  fuses  with 
the  medial  lamina,  the  two  laminae  forming  the  pterygoid  process  which  subse- 
quently unites  with  the  body  of  the  sphenoid.  (See  Fig.  176.) 

In  the  ethmoidal  region,  only  the  vomer  is  of  intramembranous  origin.  An 
ossification  center  appears  in  the  embryonic  connective  tissue  on  each  side  of 
the  perpendicular  plate  (lamina  perpendicularis)  and  these  two  centers  produce 
two  thin  plates  of  bone  which  unite  at  their  lower  borders  and  invest  the  lower 
part  of  the  perpendicular  plate.  The  portion  of  the  latter  thus  invested 
undergoes  resorption. 

The  frontal  and  parietal  bones  are  purely  of  intramembranous  origin.  About 
the  eighth  week  two  centers  of  ossification,  one  on  each  side,  appear  for  the 
frontal.  The  bones  produced  by  these  centers  unite  in  the  medial  line  to  form 
the  single  adult  bone.  In  the  event  of  an  incomplete  union  an  open  suture 
remains — the  metopic  suture.  A  single  center  of  ossification  appears  for  each 
parietal  bone  at  about  the  same  time  as  those  for  the  frontal.  The  union  of 
the  bones  which  form  the  roof  and  the  greater  part  of  the  sides  of  the  skull  does 
not  occur  till  after  birth.  The  spaces  between  them  constitute  the  sutures  and 
fontanelles  so  obvious  in  new-born  children  (Fig.  177). 

A  single  center  of  ossification  appears  in  the  embryonic  connective  tissue 
for  each  zygomatic,  lachrymal  and  nasal  bone,  all  of  which  are  of  intramem- 
branous origin. 

BONES  DERIVED  FROM  THE  BRANCHIAL  ARCHES. 

The  first  branchial  arch  becomes  divided  into  two  portions.  One  of  these, 
the  maxillary  process,  is  destined  to  give  rise  to  the  upper  jaw  and  much  of  the 
upper  lip  and  face  region.  The  other,  the  mandibular  process,  is  destined  to 
give  rise  to  the  lower  jaw,  the  lower  lip  and  chin  region,  and  two  of  the  auditory 
ossicles.  The  angle  between  the  two  processes  corresponds  to  the  angle  of  the 
mouth,  and  the  cavity  enclosed  by  the  processes  is  the  forerunner  of  the  mouth 
and  nasal  cavities.  (See  Fig.  134,  also  p.  147.)  So  far  as  the  skeletal  elements 
are  concerned,  cartilage  develops  only  in  the  mandibular  process  where  it 
forms  a  slender  bar  or  rod  known  as  MeckeVs  cartilage.  Only  a  small  part  of 
this  becomes  ossified,  the  greater  portion  of  the  mandible  being  of  intramem- 
branous origin.  No  cartilage  develops  in  the  maxillary  process.  This 
probably  indicates  a  condensation  of  development  in  man  and  the  higher 
animals,  for  among  the  lower  animals  cartilage  precedes  the  bone.  In  man  the 
maxilla  and  palate  bone  also  are  of  intramembranous  origin. 

The  palate  bone  develops  from  a  single  center  of  ossification  which  appears 
at  the  side  of  the  nasal  cavity  in  embryos  of  about  18  mm.  This  center 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM.  195 

represents  the  perpendicular  part,  the  horizontal  part  appearing  in  embryos  of 
about  24  mm.  as  an  outgrowth  from  the  perpendicular  and  not  as  a  separate 
center  of  ossification.  The  orbital  and  sphenoidal  processes  also  represent  out- 
growths from  the  primary  center  and  appear  much  later. 

Opinions  regarding  the  development  of  the  maxilla  are  at  variance.  One 
view  is  that  it  arises  from  five  centers  of  ossification.  One  of  these  centers  gives 
rise  to  that  part  of  the  alveolar  border  which  bears  the  molar  and  premolar 
teeth;  a  second  center  forms  the  nasal  process  and  that  part  of  the  alveolar  bor- 
der which  bears  the  canine  tooth;  a  third  produces  the  part  which  bears  the 
incisor  teeth;  and  the  two  remaining  centers  give  rise  to  the  rest  of  the  bone. 
All  these  parts  effect  a  firm  union  at  an  early  stage,  with  the  exception  of  the 
part  bearing  the  incisor  teeth  which  remains  more  or  less  distinct  as  the  incisive 
bane  (premaxilla,  intermaxilla) .  Another  view  arising  from  recent  work  on 


Incisive  bone  Upper  lip 

(intermaxillary) 


Primitive  choan* ^Kdfl  •£""  Lip  8roove 


Cut  surface         Palatine  processes 

FIG.  178. — Head  of  human  embryo  of  7  weeks.     His. 
Ventral  aspect  of  upper  jaw  region.     Lower  jaw  and  tongue  have  been  removed. 


human  embryos  is  that  there  are  primarily  only  two  ossification  centers;  one  of 
these  gives  rise  to  the  incisive  bone,  the  other  to  the  rest  of  the  maxilla  (Mall). 
These  centers  appear  at  the  end  of  the  sixth  week  (embryos  of  18  mm.). 

A  very  important  feature  in  the  development  of  the  maxilla  is  its  agency  in 
separating  the  nasal  cavity  from  the  mouth  cavity.  The  palatine  process  of  the 
bone  grows  medially  and  meets  and  fuses  with  its  fellow  of  the  opposite  side  in 
the  medial  line,  the  two  processes  together  thus  constituting  about  the  an- 
terior three-fourths  of  the  bony  part  of  the  hard  palate.  It  should  be  observed, 
however,  that  the  palatine  processes  do  not  meet  at  their  anterior  borders,  for 
the  incisive  bone  is  insinuated  between  them  (see  Figs.  178,  179). 


196 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  incisive  bone  is  probably  not  derived  from  the  maxillary  process  of  the  first  visceral 
arch,  but  from  the  fronto-nasal  process.  The  question  thus  arises  as  to  whether  it  is  derived 
from  both  the  middle  and  lateral  nasal  processes  or  only  from  the  middle.  According  to 
Kolliker's  view,  the  lateral  nasal  process  takes  no  part  in  the  formation  of  the  incisive  bone. 
It  is  derived  from  the  middle  process,  hence  genetically  it  is  a  single  bone  on  each  side. 
According  to  Albrecht's  view  the  incisive  bone  is  genetically  composed  of  two  parts,  one 
derived  from  the  lateral,  the  other  from  the  middle  nasal  process.  While  the  matter  is  not 
one  of  great  importance  merely  from  the  standpoint  of  development,  it  has  an  important 
bearing  on  the  question  of  certain  congenital  malformations,  e.  g.,  hare  lip,  and  will  be 
discussed  further  under  that  head  (p.  212). 

In  the  mandibular  process  of  the  first  visceral  arch,  the  mandible  develops  as 
a  bone  which  is  partly  of  intramembranous  and  partly  of  intracartilaginous 
origin.  In  the  first  place  a  rod  of  cartilage,  known  as  Meckel's  cartilage, 
forms  the  core  of  the  mandibular  process  and  extends  from  the  distal  end  of  the 
process  to  the  temporal  region  of  the  skull,  where  it  passes  between  the  tympanic 


Medial  line 
Canine  alveolus 

Molar  alveolus 


Incisive  bone 


Incisive  suture 


Palatine  process 


Palate  bone 
(horizontal  part) 


FIG.  179. — Ventral  aspect  of  hard  palate  of  human  embryo  of  80  mm.     Kollmann's  Atlas. 


bone  and  the  periotic  capsule  and  ends  in  the  tympanic  cavity  of  the  ear  (Fig. 
174).  During  the  sixth  week  of  foetal  life,  intramembranous  bone  begins  to 
develop  in  the  mandibular  process.  In  the  region  of  the  body  of  the  mandible 
the  bone  encloses  the  cartilage,  but  in  the  region  of  the  ramus  and  coronoid 
process  the  cartilage  lies  to  the  inner  side  of  the  bone.  Development  is  further 
complicated  by  the  appearance  of  cartilage  in  the  region  of  the  middle  incisor 
teeth  and  on  the  coronoid  and  condyloid  processes.  These  pieces  of  cartilage 
form  independently  of  Meckel's  cartilage  and  subsequently  are  replaced  by  the 
bone  which  constitutes  the  corresponding  parts  of  the  mandible.  The  part  of 
Meckel's  cartilage  enclosed  in  the  bone  disappears;  the  part  to  the  inner  side  of 
the  ramus  is  transformed  into  the  sphenomandibular  ligament.  (See  Fig.  180.) 
In  each  half  of  the  second  branchial  arch  a  rod  of  cartilage  develops,  which 
extends  from  the  ventro-medial  line  to  the  region  of  the  periotic  capsule.  The 


THE  CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM.  197 

proximal  end  of  this  rod  is  then  replaced  by  bone  which  fuses  with  the  temporal 
bone  and  forms  the  styloid  process.  The  distal  (ventral)  end  is  replaced  by 
bone  which  forms  the  lesser  horn  of  the  hyoid  bone.  Between  the  styloid  proc- 
ess and  the  lesser  horn,  the  cartilage  is  transformed  into  the  stylohyoid  liga- 
ment (see  Figs.  177  and  180). 

In  each  half  of  the  third  branchial  arch  a  piece  of  cartilage  develops  and 
subsequently  is  replaced  by  bone  to  form  the  greater  horn  of  the  hyoid  bone. 
The  two  horns  become  connected  at  their  ventral  ends  by  the  body  of  the  hyoid 
bone  which  is  also  a  derivative  of  the  third  arch.  Later  the  lesser  horn  fuses 
with  the  greater  horn  to  bring  about  the  adult  condition  (Fig.  180). 

In  the  ventral  parts  of  the  fourth  and  fifth  arches  pieces  of  cartilage  develop 

Incus       Malleus 


^^^^m^^^^^^^ 

Tympanic  ring 
Stylohyoid  lig. 

Cricoid  cartilage 


Thyreoid  cartilage      |  Meckel's  cartilage 

Hyoid  cartilage  (greater  horn) 

FIG.  180. — Lateral  dissection  of  head  of  human  foetus,  showing  derivatives  of  branchial 
arches  in  natural  position.     Kollmann's  Atlas. 

and  form  the  skeletal  elements  of  the  larynx.  A  more  detailed  account  of  these 
will  be  found  under  the  head  of  the  larynx  (p.  361). 

The  auditory  ossicles  are  also  derived  largely  from  the  branchial  arches,  the 
incus  and  malleus  being  derived  from  the  proximal  end  of  Meckel's  cartilage  (first 
arch) ,  the  stapes  having  a  double  origin  from  the  second  arch  and  the  embryonic 
connective  tissue  surrounding  the  periotic  capsule.  But  since  they  form  inte- 
gral parts  of  the  organ  of  hearing,  a  discussion  of  their  formation  is  best  in- 
cluded in  the  development  of  the  ear  (p.  589). 

The  accompanying  table  indicates  the  types  of  development  in  the  different 
bones  of  the  head  skeleton. 


198 


TEXT-BOOK  OF  EMBRYOLOGY. 


Bones 

Of  Intracartilaginous 
Origin 

Of  Intramembranous 
Origin 

Derived  from  Visceral 
Arches 

Occipitale. 

Pars  basilaris. 
Pars  lateralis. 
Squama  occipitalis  below 
sup.  nuchal  line. 

Squama  occipitalis  above 
sup.  nuchal  line. 

Temporale. 

Pars  mastoidea. 
Pars    petrosa,  with   proc- 
essus  sty-oideus. 

Pars  tvmpanica. 
Squama  temporalis. 

Processus  styloideus  (second 
arch). 

Sphenoidale. 

Corpus. 
Ala  parva. 
Ala  magna. 
Hamulus  pterygoideus. 

Processus  pterygoideus,  ex- 
cept hamulus    pterygoi- 
deus. 

Ethmoidale. 

Crista  galli. 
Lamina  cribrosa. 
Lamina  perpendicularis. 
Labyrinthus  ethmoidalis. 

Vomer. 

Vomer. 

Parietale. 

Parietale. 

Frontale. 

Frontale. 

Lacrimale.v 

Lacrimale. 

Nasale. 

Nasale. 

Zygoma. 

Zygoma. 

Maxilla. 

Maxilla,  with  incisivum. 

Maxilla,  except  mcisivum(  ?) 
(first  arch). 

Palatinum. 

Palatinum. 

Palatinum. 

Mandibula. 

Processus    condyloideus, 
tip  of. 
Processus  coronoideus, 
tip  of. 
Corpus,  distal  end  of. 

Processus  condyloideus,  ex- 
cept tip. 
Processus  coronoideus,  ex- 
cept tip. 
Corpus,  except  distal  end. 
Ramus. 

Mandibula  (first  arch). 

Hyoideum. 

Hyoideum 

Cornu  majus  (third  arch). 
Cornu  minus  (second  arch). 
Corpus  (third  arch). 

Ossicula 
auditus. 

Incus. 
Malleus. 
Stapes,  except  basis  (?). 

Basis  stapedis. 

Incus  (first  arch). 
Malleus   (first  arch). 
Stapes,     except    basis     (?) 
(second  arch). 

The  Appendicular  Skeleton. 

The  growth  of  the  limb  buds  and  their  differentiation  into  arm,  forearm 
and  hand,  thigh,  leg  and  foot,  along  with  the  rotation  which  they  undergo  during 
development,  have  been  discussed  in  the  chapter  on  the  external  form  of  the 
body  (p.  149).  The  metameric  origin  of  the  muscles  of  the  extremities  is 


THE   CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


199 


discussed  in  the  chapter  on  the  muscular  system  (Chap.  XI).  It  has  been 
seen  that  the  greater  part  of  the  axial  skeleton  is  derived  from  the  sclerotomes, 
is  preformed  in  cartilage,  and  maintains  its  segmental  character  throughout  life. 
It  has  also  been  seen  that  the  head  skeleton  is  in  part  preformed  in  cartilage,  is  in 
part  of  intramembranous  origin,  and  shows  but  a  trace  of  segmental  character, 
and  that  only  in  the  occipital  region  at  a  very  early  stage.  The  appendicular 
skeleton  is  derived  wholly  from  the  embryonic  connective  tissue  which  forms  the 
cores  of  the  developing  extremities,  and  shows  no  trace  of  a  segmental  character. 
Here  also,  as  in  the  axial  skeleton,  three  stages  may  be  recognized — a  blastemal, 
a  cartilaginous  (Fig.  181),  and  a  final  osseous. 

Acromion        Coracoid  process 


Scapula      &fi 


Radius 


Metacarpal  I 

__     .  : Large  multangular 

&   (trapezium) 

Navicular  (scaphoid) 
Lunate  (semilunar) 

Small  multangular 
(trapezoid) 

Metacarpal  IV 
Capitate  (os  magnum) 
Triquetral  (cuneiform) 
Hamatate  (uncifonn) 


FIG.  181. — Cartilages  of  left  upper  extremity  of  a  human  embryo  of  17  mm.     Hagen. 

In  the  region  of  the  shoulder  girdle  a  plate  of  cartilage  appears  in  the  em- 
bryonic connective  tissue  which  lies  among  the  developing  muscles  dorso-lateral 
to  the  thorax.  This  plate  of  cartilage  is  the  forerunner  of  the  scapula,  and  in 
general  resembles  it  in  shape.  During  the  eighth  week  of  fcetal  life  a  single 
center  of  ossification  appears  and  gives  rise  to  the  body  and  spine  of  the  scapula. 
After  birth  certain  accessory  centers  appear  and  produce  the  coracoid  process,  the 
supragknoidal  tuber osity,  the  acromion  process,  and  the  inferior  angle  and  verte- 
bral margin  (Fig.  182).  Later  the  supraglenoidal  fuses  with  the  coracoid  and 
forms  part  of  the  wall  of  the  glenoid  cavity.  About  the  seventeenth  year  the 
single  center  formed  by  the  union  of  these  two  fuses  with  the  rest  of  the  scapula. 


200  TEXT-BOOK  OF  EMBRYOLOGY. 

At  the  age  of  twenty  to  twenty-five  years  all  the  other  accessory  centers  unite 
with  the  rest  of  the  scapula  to  form  the  adult  bone. 

There  are  two  views  concerning  the  development  of  the  da-vide:  one  that  it 
is  of  intracartilaginous  origin,  the  other  that  it  is  of  intramembranous  origin. 
Ossification  begins  during  the  sixth  week,  possibly  from  two  centers.  It  is  true 
that  the  cartilage  that  appears  around  the  centers  is  of  a  looser  character  than 
the  ordinary  embryonic  cartilage,  but  whether  the  centers  appear  in  cartilage 
seems  not  to  have  been  determined.  At  the  age  of  fifteen  to  twenty  years  a 
sort  of  secondary  center  appears  at  the  sternal  end  of  clavicle  and  fuses  with 
the  body  about  the  twenty-fifth  year. 

The  humerus,  radius  and  ulna  are  preformed  in  cartilage  (Fig.  181)  and 
develop  as  typical  long  bones.  Ossification  begins  in  each  during  the  seventh 


Bone 


Cartilage 


FIG.  182. — Scapula  of  new-born  child,  showing  primary  center  of  ossification,  and  cartilage 
(lighter  shading)  in  which  secondary  centers  appear.     Bonnet. 

week  at  a  single  center  and  proceeds  in  both  directions  to  form  the  shaft. 
During  the  first  four  years  after  birth  epiphyseal  centers  appear  for  the  head, 
greater  and  smaller  tuberdes,  trochlea  and  epicondyles.  All  these  secondary 
centers  unite  with  the  shaft  of  the  humerus  when  the  growth  of  the  individual 
ceases.  In  the  case  of  the  radius  and  ulna  a  secondary  center  appears  at  each 
end  of  each  bone  to  form  the  epiphysis;  and  in  the  ulna  another  secondary 
center  appears  to  form  the  olecranon.  (For  the  growth  of  bones,  see  page  176). 
The  carpal  bones  are  all  preformed  in  cartilage  (Fig.  181)  but  their  develop- 
ment is  somewhat  complicated  owing  to  the  fact  that  pieces  of  cartilage  appear 
which  subsequently  may  disappear,  or  ossify  and  become  incorporated  in  other 
bones.  Primarily  seven  distinct  pieces  of  cartilage  develop  and  become  ar- 
ranged transversely  in  two  rows;  these  represent  seven  of  the  carpal  bones. 
The  proximal  row  consists  of  three  large  pieces  which  are  the  forerunners  of  the 
navicular  (radial,  scaphoid),  lunate  (intermediate,  semilunar)  and  triquetral 


THE   CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


201 


(ulnar,  pyramidal,  cuneiform) .  The  distal  row  is  composed  of  four  elements 
which  are  the  forerunners  of  the  large  multangular  (trapezium),  small  multangu- 
lar (trapezoid),  capitate  (os  magnum),  and  hamatate  or  hooked  (unciform).  In 
addition  to  the  cartilages  mentioned,  several  others  also  appear  in  an  inconstant 
way  in  different  individuals.  Two  of  these  are  important.  One  appears  on 
the  ulnar  side  of  the  proximal  row  and  is  the  forerunner  of  the  pisiform;  the 
other  is  situated  between  the  two  rows  and  may  either  disappear  entirely  or  fuse 
with  the  navicular.  Ossification  does  not  begin  in  the  carpal  cartilages  until 
after  birth;  it  begins  in  the  hamatate  and  capitate  during  the  third  year,  in  the 


Phalanges 


Metacarpals 


Large 
multangular 

Capitate 
Navicular 

Radius 


FIG.  183. — Skiagram  of  right  hand  of  5  year  old  girl.     (Courtesy  of  Dr.  Edward  Learning). 
The  ossification  centers  are  indicated  by  the  darker  areas. 

others  at  later  periods,  and  is  completed  only  when  the  growth  of  the  individ- 
ual ceases.  The  fact  that  the  hamatate  ossifies  from  two  centers  indicates 
that  it  is  probably  derived  phylogenetically  from  two  bones.  Comparative 
anatomy  teaches  that  the  accessory  cartilages  in  the  human  wrist  are  repre- 
sentatives of  structures  which  are  normally  present  in  the  lower  forms. 

The  metacarpals  and  phalanges  are  preformed  in  cartilages  which  correspond 
in  shape  to  the  adult  bones.  A  center  of  ossification  appears  in  each  cartilage 
and  produces  the  shaft  of  the  bone.  Only  one  epiphysis  develops  on  each 
metacarpal  and  phalanx.  In  each  metacarpal  it  develops  at  the  distal  end, 


202 


TEXT-BOOK  OF  EMBRYOLOGY. 


Ilium 


. 


Crural  nerve 


Pubic  bone  (cartilage) 


FIG.  184. — Cartilage  of  right  side  of  pelvic  girdle  of  a  human  embryo  of  13.6  mm. 

(5  weeks).     Peter  sen. 
The  numerals  indicate  the  vertebrae;  the  first  sacral  being  opposite  the  ilium. 


Ilium  I 


Crural  nerve 

Pubic  bone  (cartilage) 

Obturator  nerve 
Ischium 

Ischiadic  nerve 


FIG.  185. — Cartilage  of  right  side  of  pelvic  girdle  of  a  human  embryo  of  18.5  mm. 

(8  weeks).     Petersen. 

The  numerals  indicate  the  vertebrae;  the  first  and  second  sacral  being  opposite  the  ilium. 

Compare  with  Fig.  184. 


THE   CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM.  203 

except  in  the  thumb  where  it  appears  at  the  proximal  end.     In  each  phalanx  it 
develops  at  the  proximal  end  (Fig.  183). 

The  skeletal  elements  of  the  low er  extremities,  including  the  pelvic  girdle,  are 
of  intracartilaginous  origin.  Each  hip  bone  (os  coxae,  innominate  bone)  is  pre- 
formed in  cartilage  which,  in  a  general  way,  resembles  in  shape  the  adult  bone. 
The  ventral  part  of  the  pubic  cartilage  does  not  at  first  join  the  ischial;  but  by  the 
eighth  week  the  junction  is  complete,  leaving  dorsal  to  it  the  obturator  foramen. 
In  the  earliest  stages  the  long  axis  of  the  cartilage  is  nearly  at  right  angles  to  the 
vertebral  column,  and  the  ilium  lies  close  to  the  fifth  lumbar  and  first  sacral 
vertebras;  later  (eighth  week)  the  long  axis  lies  nearly  parallel  with  the  vertebral 
column  and  the  whole  cartilage  has  shifted  so  that  the  ilium  is  associated  with 
the  first  three  sacral  vertebrae  (Figs.  184  and  185). 


Pubic  bone 


Ilium 


Cartilage 


FIG.  186  — Right  os  coxae  (innominate  bone)  of  new-born  child.     Bonnet. 
Bone  is  indicated  by  darker  areas,  cartilage  by  lighter  areas. 


Ossification  begins  at  three  centers  which  correspond  to  the  ilium,  ischium 
and  pubis;  the  center  for  the  ilium  appears  during  the  eighth  week,  the  centers 
for  the  ischium  and  pubis  several  weeks  later  (Fig.  186).  The  process  of  ossifi- 
cation is  slow,  and  is  far  from  complete  at  the  time  of  birth,  for  at  that  time  the 
entire  crest  of  the  ilium,  the  bottom  of  the  acetabulum  and  all  the  region  ventral 
to  the  obturator  foramen  are  cartilaginous.  During  the  eighth  or  ninth  year 
the  ventral  parts  of  the  pubis  and  ischium  become  partly  ossified,  but  up  to  the 
time  of  puberty  the  pubis,  ischium  and  ilium  remain  separated  by  plates  of  car- 
tilage which  radiate  from  a  common  center  at  the  bottom  of  the  acetabulum. 
Soon  after  this,  the  three  bones  unite  to  form  the  single  os  coxae,  leaving  only  the 
crest  of  the  ilium,  the  pubic  tubercle  and  the  sciatic  tuber  (tuberosity  of  the 
ischium)  cartilaginous.  In  each  of  these  regions  an  accessory  ossification  cen- 


204  TEXT-BOOK  OF  EMBRYOLOGY. 

ter  appears  and  finally  fuses  with  the  corresponding  bone  about  the  twenty- 
fourth  year. 

The  femur,  tibia  andfibula  are  preformed  in  cartilage.  In  the  femur  a  center 
,of  ossification  appears  about  the  end  of  the  sixth  week  and  gives  rise  to  the 
shaft;  similar  centers  appear  in  the  tibia  and  fibula  during  the  seventh  and 
eighth  week,  respectively.  In  the  femur  a  distal  epiphyseal  center  appears 
shortly  before  birth,  and  during  the  first  year  after  birth  a  proximal  center 
appears  for  the  head.  These  centers  do  not  unite  with  the  shaft  until  the  individ- 
ual ceases  to  grow.  The  great  and  lesser  trochanters  also  have  accessory  ossifica- 
tion centers.  In  the  tibia  the  center  of  ossification  for  the  proximal  epiphysis 
appears  about  the  time  of  birth,  the  one  for  the  distal  during  the  second  year.  In 


Fibula \         — -/-- Tibia 


Calcaneus 

.Talus 


Cuboid  ~£^/7>N~NJ ^ 

Cuneiform  III*-J — /f-/7/V\  •*• Cuneiform  I 

•Cuneiform  II 


Metatarsals 
FIG.  187. — Diagram  of  cartilages  of  left  leg  and  foot  of  human  embryo  of  17  mm.     Hagen. 


the  fibula  the  epiphyseal  centers  appear  during  the  second  and  sixth  years  after 
birth.  The  cartilage  of  the  patella  appears  during  the  third  or  fourth  month 
of  fcetal  life,  and  ossification  begins  two  or  three  years  after  birth. 

The  bones  of  the  tarsus,  like  those  of  the  carpus,  are  preformed  in  pieces  of 
cartilage  which  are  arranged  in  two  transverse  rows.  The  proximal  row  con- 
sists of  three  pieces,  one  at  the  end  of  the  tibia  (tibial),  one  at  the  end  of  the 
fibula  (fibular),  and  the  third  between  the  two  (intermedial) .  At  an  early  stage 
the  tibial  and  intermedial  fuse  to  form  a  single  piece  of  cartilage  which  corre- 
sponds to  the  talus  (astragalus)  bone.  The  fibular  cartilage  corresponds  to  the 
calcaneus  (os  calcis).  The  distal  row  is  composed  of  four  pieces  of  cartilage 
which  correspond  to  the  first  cuneiform  (internal),  second  cuneiform  (middle), 
third  cuneiform  (external),  and  cuboid  (Fig.  187).  Between  the  two  rows  is  a 


THE   CONNECTIVE  TISSUES  AND   THE  SKELETAL  SYSTEM. 


205 


piece  of  cartilage  which  corresponds  to  the  navicular  (scaphoid).  Ossification 
begins  relatively  late  in  the  metatarsals.  A  center  for  the  calcaneus  appears 
during  the  sixth  month  of  foetal  life,  and  one  for  the  talus  shortly  before  birth. 
Centers  appear  in  the  cuboid  and  third  cuneiform  during  the  first  year  after 
birth,  and  in  the  first  cuneiform,  navicular  and  second  cuneiform  in  order  during 
the  third  and  fourth  years  (Figs.  188  and  189).  At  the  age  of  puberty  ossifica- 
tion is  nearly  complete  in  all  the  metatarsals.  In  the  talus  two  centers,  cor- 
responding to  the  tibial  and  intermedial,  appear,  but  soon  fuse  into  a  single 
center.  Occasionally  the  intermedial  remains  separate  and  forms  the  trigonum. 


Calcaneus 


Phalanges 


FIG.  188. — Ossification  centers  in  foot  of  a  child  9  months  old.     Hassel-wander. 

An  accessory  center  appears  in  the  calcaneus  at  the  insertion  of  the  tendon  of 
Achilles. 

The  metatarsals  and  phalanges  develop  in  a  manner  corresponding  to  the 
metacarpals  and  phalanges  (of  fingers).  Ossification  begins  in  the  metatarsals 
about  the  ninth  week,  in  the  first  row  of  (proximal)  phalanges  about  the 
thirteenth  week,  in  the  second  row  about  the  sixteenth  week  and  in  the  third 
row  (distal)  about  the  beginning  of  the  ninth  week.  Epiphyseal  centers  ap- 
pear from  the  second  to  the  eighth  year  after  birth. 

Development  of  Joints. 

The  embryonic  connective  tissue  from  which  the  connective  tissues,  includ- 
ing cartilage  and  bone,  are  developed,  at  first  forms  a  continuous  mass.  When 
cartilage  appears  it  may  form  a  continuous  mass,  as  in  the  chondrocranium,  or 


206 


TEXT-BOOK  OF  EMBRYOLOGY. 


it  may  form  a  number  of  distinct  and  separate  pieces,  as  in  the  vertebral  column, 
the  pieces  being  united  by  a  certain  amount  of  the  undifferentiated  embryonic 
connective  tissue. 

SYNARTHROSIS.  Syndesmosis. — When  ossification  begins  at  one  or  more 
centers,  either  in  cartilage  or  in  embryonic  connective  tissue,  the  centers  grad- 
ually enlarge  and  approach  each  other,  and  the  bone  so  formed  comes  in  contact 
with  the  bone  formed  in  neighboring  centers,  (a)  In  a  case  where  more  than  one 
center  appears  for  any  single  adult  bone,  they  may  come  in  contact  and  fuse  so 
completely  that  the  line  of  fusion  becomes  indistinguishable,  (b)  In  the  case  of 


Talus  (astragalus) 


Cuneiform  II 


Cuneiform  I 

Epiphysis  of 
metatarsal  I 


Metatarsal  I 


Calcaneus  -  ,  |_j  /  *\ 

(oscalcis)       \'&         ft^         T7vT~~ 


Cuboid 


Metatarsal  V  — 


Epiphysis  of 
metatarsal  V 


Phalanx 


Epiphyses  of 
phalanges 


FIG.  189. — Skeleton  of  right  foot  of  a  boy  3  years  old,  showing  ossification  centers.     Toldt. 

adjacent  bones  the  fusion  may  not  be  so  complete;  that  is,  the  two  bones  may 
simply  articulate,  leaving  a  visible  line  of  junction  or  suture.  Such  joints  are 
immovable  and  are  represented  in  the  sutures  of  the  skull. 

Synchondrosis. — In  some  cases  a  small  amount  of  embryonic  connective 
tissue  remains  between  adjacent  bones,  (a)  In  time,  this  embryonic  connective 
tissue  gives  rise  to  cartilage  which  unites  the  bones  quite  firmly,  thus  producing 
a  practically  immovable  joint,  as  in  the  case  of  the  sacro-iliac  joint,  (b)  Or  the 
cells  in  the  center  of  the  cartilage  disintegrate  or  become  liquefied  so  that  a  small 
cavity  is  produced  (articular  cavity).  This  type  of  joint  makes  possible  a  slight 
degree  of  mobility  and  is  exemplified  by  the  symphysis  of  the  pubic  bones.  Such 
a  type  is  also  represented  by  the  joints  of  the  vertebral  column.  In  place  of 
cavities,  however,  are  the  pulpy  nuclei  which  are  remnants  of  the  notochord. 


THE   CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM. 


207 


DIARTHROSIS. — Where  a  great  degree  of  mobility  is  necessary,  the  arrange- 
ment of  the  joint  is  different.  The  cells  in  the  central  part  of  the  embryonic 
connective  tissue  between  the  ends  of  adjacent  bones  (or  cartilages)  (Fig.  190) 
liquefy  so  that  a  relatively  large  cavity,  the  joint  cavity,  is  formed  (Fig.  191). 
The  liquefaction  of  the  connective  tissue  cells  may  also  extend  for  a  short  dis- 
tance along  the  sides  of  the  bones  so  that  the  joint  cavity  surrounds  the  ends 
of  the  bones  (Figs.  192  and  193).  The  origin  of  the  synovial fluid  is  not  known 


Humerus 


Radius 

FIG.  190. — Section  through  axilla  and  arm  of  a  human  embryo  of  26  mm.  (2  months).     Photograph. 
Note  the  mesenchymal  tissue  between  the  humerus  and  the  radius — the  site  of  the  elbow  joint. 

with  certainty,  but  it  is  probably  in  part  the  product  of  liquefaction  of  the  con- 
nective tissue  cells.  The  more  peripheral  part  of  the  connective  tissue  which 
encloses  the  joint  cavity  is  transformed  into  a  dense  fibrous  tissue,  the  joint 
capsule.  The  cells  lining  the  cavity  become  differentiated  into  oval  or  irregular 
cells,  among  which  is  a  considerable  amount  of  intercellular  substance.  By 
some  it  is  held  that  these  cells  form  a  continuous  single  layer  like  endothelium, 
but  the  most  recent  researches  tend  to  disprove  this.  The  cells  lining  the 


208 


TEXT-BOOK  OF  EMBRYOLOGY. 

Joint  cavity 


FlG.  191. — Longitudinal  section  of  finger  of  human  embryo  of  26  mm.  (2  months),  showing  beginning 
of  joint  cavity  between  adjacent  ends  of  phalanges.  (Photograph  from  preparation  by 
Dr.  W.  C.  Clarke.) 


FIG.  192. — From  longitudinal  section  of  finger  of  child  at  birth,  showing  developing  joint  cavity 
between  adjacent  ends  of  phalanges.  The  darker  portion  at  each  end  of  the  figure  indicates 
the  ossification  center  in  the  phalanx,  the  end  of  the  latter  (lighter  area)  being  yet  cartilagi- 
nous. The  dark  bands  at  each  side  of  the  joint  indicate  developing  ligaments.  Photograph. 


THE   CONNECTIVE   TISSUES  AND   THE  SKELETAL  SYSTEM.  209 

cavity  are  the  most  highly  differentiated,  the  cell  bodies  being  large  and  ap- 
parently swollen,  and  there  is  gradually  less  differentiation  as  the  distance  from 
the  surface  increases,  until  finally  they  merge  with  the  ordinary  type  of  con- 
nective tissue  cells  of  the  joint  capsule  (Clarke).  The  more  mobile  joints  of 
the  body  are  all  representatives  of  this  type. 

Joint  cavity 


Synovial  membrane 

FIG.  193. — From  longitudinal  section  of  finger  of  child  at  birth,  showing  joint  cavity  and  synovial 
membrane  between  adjacent  ends  of  the  first  metacarpal  and  proximal  phalanx.  Other 
description  same  as  in  Fig.  192.  Photograph. 

Anomalies. 
THE  AXIAL  SKELETON. 

THE  VERTEBRAE. — The  number  of  cervical  vertebras  in  man  is  remarkably 
constant.  Cases  where  the  number  is  but  six  are  extremely  rare.  The 
thoracic  vertebrae  may  vary  in  number  in  different  individuals  from  eleven  to 
thirteen,  twelve  being  the  usual  number.  The  lumbar  vertebrae  may  vary 
from  four  to  six,  five  being  the  usual  number.  The  sacral  vertebrae,  fused  in  the 
adult  to  form  the  sacrum,  are  usually  five  in  number,  sometimes  four,  sometimes 


210  TEXT-BOOK  OF  EMBRYOLOGY. 

six.  Occasionally  a  vertebra  between  the  lumbar  region  and  sacral  region — 
lumbo-sacral  vertebra — possesses  both  lumbar  and  sacral  characters,  one 
side  being  fused  with  the  sacrum,  the  other  side  having  a  free  transverse  process. 
Variation  occurs  frequently  in  the  coccygeal  vertebrae;  four  and  five  are  present 
with  about  equal  frequency,  more  rarely  there  are  only  three. 

The  total  number  of  true  (presacral)  vertebrae  may  be  diminished  by  one  or 
increased  by  one.  In  the  former  case  the  first  sacral  is  the  twenty-fourth  ver- 
tebra, and,  if  the  number  of  ribs  remains  normal,  there  are  only  four  lumbar 
vertebrae.  In  case  the  total  number  is  increased  by  one,  the  first  sacral  is  the 
twenty-sixth  vertebra,  and  there  are  twelve  thoracic  and  six  lumbar  or  thirteen 
thoracic  and  five  lumbar. 

From  these  facts  it  is  seen  that  variation  occurs  most  frequently  in  the  more 
caudal  portion  of  the  vertebral  column — in  the  lumbar,  sacral  and  coccygeal 
regions.  According  to  a  hypothesis  advanced  by  Rosenberg,  the  sacrum  in  the 
earlier  embryonic  stages  is  composed  of  a  more  caudal  set  of  vertebrae  than  those 
which  belong  to  it  in  the  adult,  and  during  development  lumbar  vertebras  are 
converted  into  sacral  and  sacral  vertebrae  into  coccygeal.  In  other  words,  the 
hip  bone  moves  headward  during  development  and  finally  becomes  attached  to 
vertebrae  which  are  situated  more  cranially  than  those  with  which  it  was  pri- 
marily associated.  This  change  in  the  position  of  the  pelvic  attachment,  and  the 
corresponding  reduction  in  the  total  number  of  vertebrae,  during  the  develop- 
ment of  the  individual  (i.e.,  during  ontogenetic  development)  is  believed  to 
correspond  to  a  similar  change  in  position  during  the  evolution  of  the  race  (i.e., 
during  phylogenetic  development). 

According  to  Rosenberg,  variation  in  the  adult  is  due  largely  to  a  failure 
during  ontogeny  to  carry  the  processes  of  reduction  in  the  number  of  vertebrae 
as  far  as  they  are  usually  carried  in  the  race,  or  to  their  being  carried  beyond  this 
point. 

The  coccygeal  vertebrae  apparently  represent  remnants  of  the  more  exten- 
sively developed  caudal  vertebrae  in  lower  forms.  In  human  embryos  of  8  to 
16  mm.,  when  the  caudal  appendage  is  at  the  height  of  its  development,  there 
are  usually  seven  anlagen  of  coccygeal  vertebrae.  During  later  development  this 
number  becomes  reduced  by  fusion  of  the  more  distally  situated  anlagen  to  the 
smaller  number  in  the  adult.  This  process  of  reduction  varies  in  different  in- 
dividuals, so  that  five  or  four,  rarely  three,  coccygeal  vertebrae  may  be  the  result. 
In  cases  where  children  are  born  with  distinct  caudal  appendages  there  is  no 
good  evidence  that  the  number  of  coccygeal  vertebrae  is  increased,  although  the 
coccyx  may  extend  into  the  appendage. 

THE  RIBS. — Occasionally  in  the  adult  a  rib  is  present  on  one  side  or  on 
each  side  in  connection  with  the  seventh  cervical  vertebra  (cervical  rib),  or  in 
connection  with  the  first  lumbar  vertebra  (lumbar  rib).  There  seems  to  be  no 


THE   CONNECTIVE  TISSUES  AND  THE  SKELETAL  SYSTEM.  211 

case  on  record  where  cervical  and  lumbar  ribs  are  present  in  the  same  individual. 
The  cervical  rib  may  vary  between  a  small  piece  of  bone  connected  with  the 
transverse  process  of  the  vertebra  and  a  well  developed  structure  long  enough  to 
reach  the  sternum.  There  are  also  great  variations  in  the  size  of  the  lumbar  rib. 
In  case  the  number  of  ribs  is  normal,  the  last  (twelfth)  may  be  rudimentary. 

The  eighth  costal  cartilage  not  infrequently  unites  with  the  sternum.  Oc- 
casionally the  seventh  costal  cartilage  fails  to  fuse  with  the  sternum,  owing  to 
the  shortening  of  the  latter,  but  meets  and  fuses  with  its  fellow  of  the  opposite 
side  in  the  midventral  line. 

The  above  mentioned  anomalies  can  be  referred  back  to  aberrant  develop- 
ment. Primarily  costal  processes  appear  in  connection  with  the  cervical,  lum- 
bar and  sacral  vertebrae.  Normally  these  processes  fuse  with  and  finally  form 
parts  of  the  vertebrae  (p.  185).  In  some  cases,  however,  the  seventh  cervical  or 
the  first  lumbar  processes  develop  more  fully  and  form  more  or  less  distinct  ribs. 

As  an  explanation  of  these  variations  in  the  number  of  ribs,  it  has  been  sug- 
gested that  there  is  a  tendency  toward  reduction  in  the  total  number  of  ribs,  and 
that  supernumerary  ribs  represent  the  result  of  a  failure  to  carry  the  reduction  as 
far  as  the  normal  number.  In  case  the  twelfth  rib  is  rudimentary,  the  reduction 
has  been  carried  beyond  the  normal  limit.  This  hypothesis  is  a  corollary  to  the 
hypothesis  regarding  the  variations  in  the  number  of  vertebrae.  (See  under 
"The  Vertebrae.") 

THE  STERNUM. — Certain  anomalous  conditions  of  the  sternum  can  also  be 
explained  by  reference  to  development.  The  condition  known  as  cleft  sternum, 
in  which  the  sternum  is  partially  or  wholly  divided  into  two  longitudinal  bars 
by  a  medial  fissure,  represents  the  result  of  a  failure  of  the  two  bars  to  unite  in 
the  midventral  line  (p.  185,  see  also  Fig.  168).  This  is  sometimes  associated 
with  ectopia  cordis  (p.  286).  The  xyphoid  process  may  also  be  bifurcated  or 
perforated,  according  to  the  degree  of  fusion  between  the  two  primary  bars 
(p.  186). 

Suprasternal  bones  may  be  present.  They  represent  the  ossified  episternal 
cartilages  which  have  failed  to  unite  with  the  manubrium  (p.  186).  Morpho- 
logically the  suprasternal  bones  possibly  represent  the  omosternum,  a  bone 
situated  cranially  to  the  manubrium  in  some  of  the  lower  Mammals. 

THE  HEAD  SKELETON. — The  skull  is  sometimes  decidedly  asymmetrical. 
Probably  no  skull  is  perfectly  symmetrical.  The  condition  which  most  fre- 
quently accompanies  the  irregular  forms  of  skulls  is  premature  synosteosis  or 
premature  closure  of  certain  sutures.  The  cranial  bones  increase  in  size  prin- 
cipally at  their  margins,  and  when  a  suture  is  prematurely  closed  the  growth  of 
the  skull  in  a  direction  at  right  angles  to  the  line  of  suture  is  interfered  with. 
Consequently  compensatory  growth  must  take  place  in  other  directions.  Thus 
if  the  sagittal  suture  is  prematurely  closed  and  transverse  growth  prevented, 


212  TEXT-BOOK  OF  EMBRYOLOGY. 

increase  occurs  in  the  vertical  and  longitudinal  directions.  This  results  in  the 
vault  of  the  skull  becoming  heightened  and  elongated,  like  an  inverted  skiff,  a 
condition  known  as  scaphocephaly.  After  premature  closure  of  the  coronal 
suture,  growth  takes  place  principally  upward  and  gives  rise  to  acrocephaly.  In 
case  only  one-half  the  coronal  or  lambdoidal  suture  is  closed,  the  growth  is 
oblique  and  results  in  plagiocephaly. 

A  suture — the  metopic  suture — sometimes  exists  in  the  medial  line  between 
the  two  halves  of  the  frontal  bone,  a  condition  known  as  metopism.  This  is  due 
to  an  imperfect  union  of  the  two  plates  of  bone  produced  by  the  two  centers  of 
ossification  in  the  frontal  region  (p.  194). 

Certain  malformations  in  the  face  region  and  in  the  roof  of  the  mouth  are 
brought  about  by  defective  fusion  or  complete  absence  of  fusion  between  certain 
structures  during  the  earlier  embryonic  stages.  The  maxillary  process  of  the 
first  branchial  arch  sometimes  fails  to  unite  with  the  middle  nasal  process 
(Kolliker's  view,  p.  196;  see  also  Fig.  136).  The  result  is  a  fissure  in  the 
upper  lip,  a  condition  known  as  hare  lip,  which  may  or  may  not  be  accompanied 
by  a  cleft  in  the  alveolar  process  of  the  maxilla,  extending  as  far  as  the  incisive 
(palatine)  foramen.  The  same  result  may  be  produced  by  a  defective  fusion 
between  the  middle  nasal  process  and  the  lateral  nasal  process  (Albrecht's  view, 
p.  196;  see  also  Fig.  136).  Hare  lip  may  be  either  unilateral  (single)  or  bilateral 
(double),  accordingly  as  defective  fusion  occurs  on  one  or  both  sides,  but  never 
medial. 

Occasionally  the  palatine  process  of  the  maxillary  process  fails  to  meet  not 
only  its  fellow  of  the  opposite  side,  but  also  the  vomer  (see  Fig.  1 79) .  The  result 
is  a  cleft  in  the  hard  palate,  a  condition  known  as  cleft  palate.  This  malforma- 
tion may  be  unilateral  or  bilateral,  but  not  medial.  Sometimes  the  cleft  extends 
into  the  soft  palate  where  it  occupies,  however,  a  medial  position. 

Cleft  palate  may  accompany  hare  lip,  or  either  may  exist  without  the  other, 
depending  upon  the  degree  of  fusion  between  the  processes  mentioned  above. 
In  bilateral  hare  lip,  with  or  without  cleft  palate,  the  incisive  (intermaxillary) 
bone  is  sometimes  pushed  forward  by  the  vomer  and  projects  beyond  the  surface 
of  the  face,  a  condition  known  as  "wolf's  snout." 

The  causes  underlying  the  origin  of  hare  lip  and  cleft  palate  are  very  obscure. 

THE  APPENDICULAR  SKELETON. 

THE  HUMERUS. — On  the  medial  side  of  the  humerus,  just  proximal  to  the 
medial  condyle,  there  is  not  infrequently  a  small  hook-like  process  directed 
distally — the  supracondyloid  process.  This  process  represents  a  portion  of  bone 
which  in  some  of  the  lower  mammals  (cat,  for  example)  joins  the  internal 
condyle  and  completes  the  supracondyloid  foramen,  through  which  the  median 
nerve  and  brachial  artery  pass. 


THE  CONNECTIVE  TISSUES  AND   THE  SKELETAL   SYSTEM.  213 

THE  CARPAL  BONES. — Occasionally  an  os  centrale  is  present  in  addition  to 
the  usual  carpal  bones.  It  is  situated  on  the  dorsal  side  of  the  wrist  between  the 
navicular,  capitate  and  small  multangulum.  In  the  embryo  an  additional  piece 
of  cartilage  is  of  constant  occurrence  in  this  location,  but  usually  disappears 
during  later  development;  in  cases  where  it  persists,  ossification  takes  place 
to  form  the  os  centrale.  In  some  of  the  apes  the  os  centrale  is  of  constant 
occurrence  in  the  adult. 

THE  FEMUR. — The  gluteal  tuberosity  (ridge)  sometimes  projects  like  a 
comb,  forming  the  so-called  third  trochanter,  a  structure  homologous  with  the 
third  trochanter  in  the  horse  and  some  other  mammals. 

THE  TARSAL  BONES. — Cases  have  been  recorded  in  which  the  total  number 
of  tarsal  bones  was  reduced,  owing  to  congenital  synosteosis  (fusion)  of  the 
calcaneus  (os  calcis)  and  scaphoid  (navicular),  of  the  talus  (astragalus)  and 
calcaneus,  or  of  the  talus  and  scaphoid.  Occasionally  an  additional  bone — the 
trigonum — is  present  at  the  back  of  the  talus.  In  the  embryo,  the  talus  ossifies 
from  two  centers  which  normally  fuse  at  an  early  stage  into  a  single  center. 
The  trigonum  probably  represents  a  bone  produced  by  one  of  the  centers  which 
has  remained  separate. 

POLYDACTYLY. — This  anomaly  consists  of  an  increase  in  the  number  of 
fingers  or  toes,  or  both.  Any  degree  of  variation  may  exist  from  a  supernum- 
erary finger  or  toe  to  a  double  complement  of  fingers  or  toes.  The  causes  under- 
lying  the  origin  of  such  anomalies  are  not  clear.  Some  assign  the  supernumer- 
ary digits  to  the  category  of  pathological  growths  or  neoplasms,  linking  them 
with  partial  duplicate  formations.  Others  explain  the  extra  digits  on  the  ground 
of  atavism  or  reversion  to  an  ancestral  type.  The  latter  explanation  assumes 
an  ancestral  type  with  more  than  five  digits.  But  neither  zoology  nor  paleon- 
tology has  found  any  vertebrate  form,  above  the  Fishes,  which  normally  pos- 
sesses more  than  five  digits  on  each  extremity.  Consequently  one  must  refer  to 
the  Fishes  for  some  ancestral  type  to  explain  the  existence  of  more  than  five 
digits.  Going  back  so  far  in  phylogenetic  history,  no  certainty  whatever  can  be 
attached  to  the  origin  of  supernumerary  digits,  for  it  is  not  even  known  from 
what  fins  the  extremities  of  the  higher  forms  are  derived.  Still  another  view 
regarding  the  origin  of  supernumerary  digits  is  that  they  are  due  to  certain  ex- 
ternal influences  among  which  the  most  important  is  the  mechanical  impression 
of  amniotic  folds  or  bands.  This,  however,  could  not  be  the  sole  cause  of 
polydactylism,  since  such  malformations  are  common  in  amphibian  embryos 
where  no  amnion  is  present. 

References  for  Further  Study. 

ADOLPHI,  H. :  Ueber  die  Variationen  des  Brustkorbes  und  der  Wirbelsaule  des  Menschen. 
Morph.  Jahrbuch,  Bd.  XXIII,  1905. 


214  TEXT-BOOK  OF    EMBRYOLOGY. 

BADE,  P.:  Die  Entwickelung  des  menschlichen  Skeletts  bis  zur  Geburt.  Arch.  /.  mik. 
Anat.t  Bd.  LV,  1900. 

BARDEEN,  C.  R.:  Numerical  Vertebral  Variations  in  the  Human  Adult  and  Embryo. 
Anat.  Anz.,  Bd.  XXV,  1904. 

BARDEEN,  C.  R.:  Studies  of  the  Development  of  the  Human  Skeleton.  American 
Jour,  of  Anat.,  Vol.  IV,  1905. 

BARDEEN,  C.  R.:  The  Development  of  the  Thoracic  Vertebra  in  Alan.  American 
Jour,  of  Anat.,  Vol.  IV,  1*905. 

BARTELS,  M.:  Ueber  Menschenschwanze.     Arch.  /.  Anthropol.,  Bd.  XII. 

BERNAYS,  A.:  Die  Entwickelungsgeschichte  des  Kniegelenkes  des  Menschen  mit 
Bemerkungen  iiber  die  Gelenke  im  allgemeinen.  Morph.  Jahrbuch,  Bd.  IV,  1878. 

BOLL,  F.:  Die  Entwickelung  des  fibrillaren  Bindegewebes,  Arch.  /.  mik.  Anat.,  Bd. 
VIII,  1872. 

BOLK,  L.:  Beziehungen  zwischen  Skelett,  Muskulatur  und  Nerven  der  Extremitaten, 
etc.  Morph.  Jahrbuch,  Bd.  XXI,  1894. 

BONNET,  R.:  Lehrbuch  der  Entwickelungsgeschichte.     Berlin,  1907. 

BRATJS,  H.:  Die  Entwickelung  der  Form  der  Extremitaten  und  des  Extremitatenskeletts. 
In  Hertwig's  Handbuch  der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd. 
Ill,  Teil  II,  1904. 

BROWN,  ALFRED  J.:  The  Development  of  the  Vertebral  Column  in  the  Domestic 
Cat.  Anat.  Record,  Vol.  X,  No.  3,  1916. 

FAWCETT,  E.:  On  the  Early  Stages  in  the  Ossification  of  the  Pterygoid  Plates  of  the 
Sphenoid  Bone  of  Man.  Anat.  Anz.,  Bd.  XXVI,  1905. 

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1905. 

FAWCETT,  E.:  On  the  Development,  Ossification  and  Growth  of  the  Palate  Bone.  Jour, 
of  Anat.  and  Physiol.,  Bd.  XL,  1906. 

FLEMMING,  W. :  Die  Histogenese  der  Stiitzsubstanzen  der  Bindesubstanzgruppe.  In 
Hertwig's  Handbuch  der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  Ill, 
Teil  II,  1901. 

FLEMMING,  W.:  Morphologic  der  Zelle.  Ergebnisse  der  Anat.  u.  Entwick.,  Bd.  VII, 
1897. 

GAUPP,  E.:  Alte  Probleme  und  neuere  Arbeiten  iiber  den  Wirbeltierschadel.  Ergebnisse 
der  Anat.  u.  Entwick.,  Bd.  X,  1901. 

GAUPP,  E.:  Die  Entwickelung  des  Kopfskeletts.  In  Hertwig's  Handbuch  der  vergleich. 
u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  Ill,  Teil  II,  1905. 

GEGENBAUR,  C.:  Die  Metamerie  des  Kopfes  und  die  Wirbeltheorie  des  Kopfskeletts. 
Morph.  Jahrbuch,  Bd.  XIII,  1887. 

GR^EFENBERG,  E.:  Die  Entwickelung  der  Knochen,  Muskeln  und  Nerven  der  Hand 
und  der  fiir  die  Bewegungen  der  Hand  bestimmten  Muskeln  des  Unterarms.  Anat.  Hefte, 
Heft  XC,  1905. 

HAGEN,  W.:  Die  Bildung  des  Knorpelskeletts  beim  menschlichen  Embryonen.  Arch. 
j.  Anat.  u.  Physiol.,  Anat.  Abth.,  1900. 

HANSEN,  C.:  Ueber  die  Genese  einiger  Bindegewebsgrundsubstanzen.  Anat.  Anz., 
Bd.  XVI,  1899. 

HASSELWANDER,  A.:  Untersuchungen  iiber  die  Ossification  des  menschlichen  Fuss- 
skeletts.  Zeitschr.  f.  Morphol.  u.  Anthropol.,  Bd.  V,  1903. 

HERTWIG,  O.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  u.  der  Wirbeltiere. 
Jena,  1906. 


THE   CONNECTIVE  TISSUES  AND  THE  SKELETAL   SYSTEM.  215 

JAKOBY,  M.:  Beitrag  zur  Kenntniss  des  menschlichen  Primordialcraniums.  Arch.  f. 
mik.  Anal.,  Ed.  XLIV,  1894. 

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Anat.  Abth.,  1891. 

KEIBEL,  F.:  Zur  Entwickelungsgeschichte  der  Chorda  bei  Saugern.  Arch.  f.  Anat. 
u.  Physiol.,  Anat.  Abth.,  1889. 

KEIBEL,  F.,  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  Vol.  I,  1910.     Chap.  XI. 

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Ed.  LIII,  1899. 


CHAPTER  X. 

THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM. 
THE  BLOOD  VASCULAR  SYSTEM. 

The  blood  vessels  constitute  such  an  extensive  and  complex  system  that 
it  is  obviously  beyond  the  scope  of  this  book  to  consider  the  entire  system  in 
detail.  Consequently  attention  must  be  directed  only  to  the  develop- 
ment of  the  main  channels,  including  the  heart,  and  to  the  principles  of 
vessel  formation. 


a  b 

FIG.  194. — Surface  views  of  chick  blastoderms.     Rtickert,  Hertwig. 

a,  Blastoderm  with  primitive  streak  and  head  process;  showing  blood  islands  (dark  spots  in 

crescent-shaped  area  in  lower  part  of  figure). 

b,  Blastoderm  with   6   pairs  of  primitive  segments.     Reticulated  appearance  is  due  to  blood 

islands  (dark  spots)  and  to  developing  vessels,  the  entire  reticulated  area  being  the  area 
vasculosa. 

The  formation  of  blood  vessels  in  all  the  higher  vertebrates  including 
mammals  begins  in  the  opaque  area  of  the  blastoderm  (area  opaca)  while 
the  germ  layers  still  lie  flat.  Toward  the  end  of  the  first  day  of  incubation 
in  the  chick,  about  the  time  the  primitive  streak  reaches  the  height  of  its 

216 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


217 


development,  the  peripheral  part  of  the  area  opaca  caudal  and  lateral  to  the 
primitive  streak  presents  a  mpttled  appearance  (Fig.  1940).  This  indicates 
the  beginning  of  the  area  vasculosa,  which  subsequently  extends  forward  in 
the  peripheral  portion  of  the  opaque  area,  lateral  to  the  developing  body, 
and  becomes  reticulated  in  appearance  (Fig.  1946). 

Sections  of  the  blastoderm  show  that  the  mottled  surface  appearance  is 
due  to  clusters  of  cells  amidst  the  mesoderm,  known  as  blood  islands  (Fig. 
195).  These  are  composed  of  rounded  cells  which  have  developed  from  the 
branched  mesodermal  (mesenchymal)  cells,  and  are  situated  in  close  apposi- 
tion to  the  entoderm.  Subsequently,  when  the  ccelom  appears  in  this  region, 
they  lie  in  the  visceral,  or  splanchnic,  layer  of  mesoderm  (Fig.  196). 


Ectoderm' 
Mesoderm 


Entoderm 
(yolk  cells) 


Blood  island 


FIG.  195. — Section  of  blastoderm  (area  opaca)  of  chick  of  27  hours'  incubation.     Photograph. 

The  early  changes  that  occur  in  the  blood  islands  are  important  as  re- 
gards both  developing  vessels  and  blood  cells.  The  superficial  cells  of  an 
island  are  transformed  into  flat  cells  placed  edge  to  edge  which  surround 
the  remaining  rounded  cells.  The  flat  cells  constitute  the  endothelium  of  a 
primitive  blood  space,  while  the  cells  within  the  space  comprise  primitive 
blood  cells  (Fig.  196).  These  early  spaces  in  the  area  vasculosa  join  one 
another  and  become  continuous  to  form  a  net-work,  or  plexus,  of  channels 
to  which  is  due  the  reticulated  appearance  referred  to  above  (Fig.  1946). 
This  is  known  as  the  vitelline  plexus.  The  groups  of  primitive  blood  cells 
within  the  channels  will  be  considered  in  detail  in  a  subsequent  section 
(page  268). 

During    the    second    day    of   incubation   in    the    chick    the    peripheral 


218 


TEXT-BOOK  OF  EMBRYOLOGY 


channels  of  the  vascular  area  unite  to  form  a  vessel — the  sinus  terminalis — • 
which  is  continuous  around  the  border  except  at  the  head  end  of  the  embryo 
(Fig.  197).  At  the  same  time  the  vascularization  of  the  visceral  layer  of 
mesoderm  gradually  extends  through  the  clear  area  of  the  blastoderm 
(area  pellucida)  toward  and  finally  into  the  embryonic  body.  Reaching 
the  region  just  lateral  to  the  notocord,  the  vessels  unite  longitudinally  in  the 
embryo  to  form  a  continuous  channel,  the  primitive  aorta,  which  thus  con- 
stitutes a  natural  selvage  to  the  vascular  area  on  each  side  of  the  blastoderm 
(Fig.  197).  Some  of  the  channels  of  the  vitelline  plexus  increase  in  size 
and  coalesce  to  form  a  large  trunk  which  is  a  branch  of  the  primitive  aorta 


Ccelom 


Parietal  mesoderm 


Ectoderm 


Visceral  mesoderm 


Blood  islands 


FIG.  196. — Section  of  blastoderm  of  chick  of  42  hours'  incubation.  Photograph.  The  cells  of 
the  blood  islands  are  differentiated  into  primitive  blood  cells  and  the  endothelium  of 
the  vessels. 

on  each  side  and  leads  off  into  the  smaller  vessels  in  the  peripheral  part  of 
the  vascular  area.  This  trunk  is  known  as  the  vitelline,  or  omphalomesenteric, 
artery  and  is  at  first  located  near  the  caudal  end  of  the  embryo.  When  cir- 
culation is  established  through  contractions  of  the  heart  it  carries  blood 
from  the  aorta  to  the  surface  of  the  yolk  sac  (Fig.  197).  Other  channels  of 
the  vitelline  plexus  nearer  the  head  end  of  the  embryo  likewise  form  a  large 
trunk,  the  vitelline,  or  omphalomesenteric,  vein  which  collects  the  blood  from 
the  surface  of  the  yolk  sac  and  conveys  it  to  the  heart  (Fig.  197). 

So  long  as  the  germ  layers  lie  flat  the  two  primitive  aortae  remain  separate, 
but  with  the  ventral  flexion  and  fusion  of  the  germ  layers  to  form  the  tubular 
body  the  aortae  fuse  into  a  single  medial  vessel,  the  dorsal  aorta,  except  in 
the  cervical  region  where  the  two  original  vessels  persist  as  the  dorsal  aortic 
roots.  The  proximal  ends  of  the  vitelline  arteries  also  fuse  into  a  single 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


219 


trunk,  the  two  vitelline  veins,  however,  remaining  separate.  In  each 
branchial  arch  on  each  side  a  vessel  develops  which  joins  with  the  corre- 
sponding dorsal  aortic  root.  These  vessels — the  aortic  arches — arise  from  a 
single  vessel  on  each  side  ventral  to  the  pharynx  which  is  known  as  the 
ventral  aortic  root.  The  two  ventral  aortic  roots  arise  from  a  single  medial 


FIG.  197. — Dorsal  surface  view  of  chick  embryo  with  18  segments,  including  the  area  vasculosa. 
Photograph,  X  15.  The  blood  vessels  were  injected  with  India  ink,  the  dark  blotch  in 
the  upper  left  corner  indicating  some  ink  which  escaped  during  the  injection. 

vessel,  the  aortic  trunk,  or  truncus  arteriostis,  which  in  turn  is  a  continuation 
of  the  early  tubular  heart. 

The  heart,  having  developed  and  become  a  contractile  organ  in  the 
meantime,  receives  the  blood  in  its  caudal  end  through  the  vitelline  veins 
and  ejects  it  from  its  cephalic  end  through  the  aortic  trunk.  The  blood 
then  passes  through  the  aortic  arches  to  the  dorsal  aorta  whence  it  is  dis- 
tributed to  the  vitelline  plexus  by  the  vitelline  arteries.  The  blood  is 


220 


TEXT-BOOK  OF  EMBRYOLOGY 


collected  by  tributaries  of  the  vitelline  veins  and  carried  to  the  heart.  Thus 
the  vitelline  (yolk)  circulation  is  completed  (Fig.  198).  From  this  time  on, 
the  area  vasculosa  gradually  enlarges,  as  the  germ  layers  extend  farther  and 
farther  around  the  yolk,  until  it  eventually  surrounds  the  whole  yolk  mass. 
In  mammals,  as  in  the  chick,  the  vascular  rudiments  develop  first  in  the 
extraembryonic  portion  of  the  mesoderm  as  clusters  of  cells  which  give  the 
area  opaca  a  mottled  appearance  on  surface  view.  This  soon  changes  to  a 
reticulated  appearance  as  the  cell  clusters  give  rise  to  primitive  blood  spaces 
which  join  one  another  to  form  a  plexus  of  channels.  This  plexus  gradually 


Aortic  arches 


Sinus  terminalis 


Heart 


Sinus      // 
terminalis ' /;/ 


Ant.  cardinal 
vein 

Aorta 


Right  vitelline  vein 

Right  vitelline  artery 


If       Duct  cf  Cuviev 

Pest,  cardinal  vein 
Left  vitelline  artery 


Left  vitelline  vein 


FIG.  198. — Diagram  of  the  vitelline  (yolk)  circulation  of  a  chick  embryo  at  the  end  of 
the  third  day  of  incubation.     Ventral  view.     Balfotir. 

extends  across  the  area  pellucida  toward  the  embryo  and  terminates  in  a 
natural  selvage  as  the  primitive  aorta  on  each  side  of  the  median  line.  The 
vitelline  arteries  and  veins  are  formed  out  of  the  plexus  and,  with  the  heart, 
aortic  arches  and  dorsal  aorta  as  in  the  chick,  constitute  the  vitelline  cir- 
culatory system  (Fig.  199).  The  vascular  area  in  some  mammals  gradually 
enlarges  until  it  embraces  the  entire  yolk  sac  (Fig.  200). 

It  is  seen  from  the  foregoing  account  that  the  earliest  circulation  is  asso- 
ciated with  the  yolk  sac.  In  animals  below  the  mammals,  where  a  large 
amount  of  yolk  is  present  in  the  sac,  the  vitelline  circulation  is  of  prime 


THE   DEVELOPMENT  OF   THE   VASCULAR   SYSTEM 


221 


FIG.  199. — Surface  view  of  area  vasculosa  of  a  rabbit  embryo  of  1 1  days,     van  Beneden  and  Julin. 
The  vessel  around  the  border  is  the  sinus  terminalis;  the  two  large  vessels  above  the  embryo  are 

the  vitelline   (omphalomesenteric)   veins ;    the    two    large  vessels  converging  below  the 

embryo  are  the  vitelline  (omphalomesenteric)  arteries. 


Chorionic  villi 

FIG.  200. — Human  embryo  of  3.2  mm.     His.     The  arrows  indicate  the  direction 

of  the  blood  current. 


222 


TEXT-BOOK  OF   EMBRYOLOGY 


importance  in  supplying  the  growing  embryo  with  nutritive  materials.  In 
mammals  the  vitelline  circulatory  system  develops  as  extensively  as  in  the 
lower  forms  but,  since  little  yolk  is  present,  does  not  assume  the  same  impor- 
tant role  of  carrying  food  supply ;  yet  the  portions  of  the  vessels  inside  the  em- 
bryo, viz. :  the  heart,  aortic  arches,  aorta,  the  proximal  part  of  the  vitelline 
artery,  and  the  vitelline  veins,  form  parts  of  the  permanent  vascular  system. 
In  reptiles  and  birds  a  second  set  of  vessels  develops  in  connection  with 
the  allantois  and  serves  to  carry  away  the  waste  products  of  the  body  and 
deposit  them  in  that  sac-like  structure.  Two  arteries,  one  on  each  side, 


Gut 


Umbilical  vein 


Amnion 


Allantois 


Yolk  stalk 


Umbilical  artery 
Umbilical  vein 

Amnion 


Chorionic  villi 


FIG.  201. — Diagram  of  the  umbilical  vessels  in  the  belly  stalk  and  chorion.     Kollmann's  Atlas. 

arise  as  branches  of  the  dorsal  aorta  near  its  caudal  end  and  pass  out  of  the 
body  along  with  the  allantoic  duct  to  ramify  upon  the  surface  of  the  allantois. 
These  are  the  umbilical,  or  allantoic,  arteries.  The  blood  is  collected  and 
carried  back  by  the  umbilical  veins  which  pass  along  the  allantoic  duct  to  the 
body  and  then  forward,  one  on  each  side,  through  the  somatic  layer  of 
mesoderm  to  join  the  ducts  of  Cuvier.  The  duct  of  Cuvier,  formed  on  each 
side  by  the  junction  of  the  anterior  and  posterior  cardinal  veins,  which  will 
be  considered  in  a  subsequent  section,  pour  their  blood  into  the  sinus  venosus. 
This  venous  trunk  is  formed  by  the  junction  of  the  ducts  of  Cuvier  with  the 
vitelline  veins  and  empties  directly  into  the  heart. 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


223 


In  mammals  in  general  the  allantois  is  a  rudimentary  structure  incapable 
of  receiving  the  total  waste  of  the  embryo.  The  umbilical  (allantoic) 
vessels  develop,  however,  as  in  reptiles  and  birds  but  become  associated 
through  the  belly  stalk  with  the  placenta  which  establishes  communication 
between  the  embryo  and  the  mother  (Fig.  201).  The  vessels  within  the 
embryo  are  at  first  disposed  in  the  same  manner  as  in  the  lower  forms, 


Int.  carotid  artery 


Vertebral  artery 


Vitelline  vein 
Vitelline  artery 

Umbilical  vein 

Umbilical 

arteries 


Duct  of  Cuvier 


Post,  cardinal 
vein 


\ 


'Aorta 


Post,  cardinal  vein 


FIG.  202. — Reconstruction  of  a  human  embryo  of   7  mm.     Mall. 

Arteries  represented  in  black.  A.V.,  Auditory  vesicle;  B,  bronchus;!,,  liver;  K,  anlage  of 
kidney;  T,  thyreoid  gland;  III-XII,  cranial  nerve  roots;  i,  2,  3,  4,  branchial  grooves;  i, 
8,  12,  5  (on  spinal  nerve  roots),  ist  and  8th  cervical,  i2th  dorsal,  5th  lumbar  spinal  nerves 
respectively.  Dotted  outlines  represent  limb  buds. 

the  umbilical  arteries  arising  from  the  caudal  portion  of  the  aorta  and  the 
umbilical  veins  passing  forward  in  the  ventro-lateral  body  wall  to  join  the 
ducts  of  Cuvier.  With  the  formation  of  the  umbilical  cord  the  two  umbilical 
veins  within  this  structure  fuse  into  a  single  vessel  (Fig.  202).  The  later 
changes  in  the  umbilical  veins  are  most  conveniently  considered  subsequently. 
In  mammals  in  general  the  umbilical  (allantoic)  circulatory  system 
performs  a  two-fold  function.  The  blood  carries  to  the  placenta  the  waste 


224  TEXT-BOOK   CF   EMBRYOLOGY 

products  of  the  embryo  for  deposition  in  the  maternal  circulation,  the  waste 
in  the  lower  forms  (reptiles  and  birds)  being  deposited  in  the  allantois. 
The  blood  carries  from  the  placenta  the  food  materials  derived  from  the 
maternal  circulation,  the  food  in  the  lower  forms  being  taken  from  the  yolk 
sac  and  conveyed  to  the  embryo  by  the  vitelline  vessels. 

Principles  of  Vasculogenesis. — Upon  the  thesis  that  tissues  in  general 
must  receive  materials  which  they  build  up  into  their  own  substances  and 
must  discharge  the  products  of  their  activities,  the  vascular  channels  of 
the  body  can  be  considered  as  structural  expressions  of  this  functional 
necessity.  For  instance,  a  muscle  which  acts  must  receive  materials  to 
compensate  it  for  its  loss  and  must  discharge  the  waste  products  that  result 
from  its  action,  and  the  blood  vessels  are  peculiarly  adapted  to  these  func- 
tions. The  lymph  vessels,  too,  similar  in  structure  to  the  blood  vessels, 
although  efferent  relative  to  the  tissues,  play  their  part  in  conveying  the 
products  of  metabolism. 

Much  controversy  has  arisen  over  the  actual  genesis,  or  origin,  of  blood 
vessels  and  lymphatics,  and  as  yet  the  opposing  views  have  not  been  recon- 
ciled. In  brief  there  are  two  views:  One  that  with  a  few  exceptions  every 
vessel  in  the  body  develops  as  a  sprout  from  another  vessel,  that  is,  the 
endothelium  arises  from  preexisting  endothelium  by  proliferation  of  its  own 
cells;  the  other  that  vessels  in  general  arise  in  situ,  that  is,  the  lumen  of  a 
vessel  represents  an  intercellular  tissue  space,  or  several  such  spaces,  whose 
bordering  cells  have  been  transformed  into  the  characteristic  endothelial 
cells,  and  as  a  corollary,  the  continuity  of  a  given  vessel  results  from  the 
union  of  such  spaces.  According  to  the  latter  view,  the  whole  vascular 
system  represents  intercellular  tissue  spaces  which,  with  their  lining  of 
flattened  cells,  have  united  to  form  a  set  of  continuous  channels. 

In  the  case  of  either  view  it  is  recognized  that  the  first  vessels  appear 
in  the  opaque  area  of  the  blastoderm.  Here  the  blood  islands  originate  as 
clusters  of  cells  amidst  the  mesoderm,  differentiating  from  mesenchymal 
elements  in  close  approximation  to  the  entoderm  (Fig.  195).  The  superficial 
cells  of  the  clusters  are  then  transformed  into  flat  cells  placed  edge  to  edge 
to  form  the  endothelial  wall  of  a  primitive  blood  space.  These  blood 
spaces  join  one  another  and  thus  form  a  net-work  of  channels.  From  this 
point  in  development  the  two  views  diverge. 

The  evidence  adduced  in  favor  of  either  theory  is  too  great  in  volume 
to  set  down  here.  The  advocates  of  the  theory  of  sprouting  of  the  endo- 
thelium lay  stress  upon  the  evidence  of  injected  specimens.  By  injecting 
developing  blood  vessels  at  successive  stages  it  is  found  that  the  vascular 
field  gradually  becomes  larger,  and  the  inference  is  that  the  individual 
channels  are  extending  farther  and  farther  from  the  focus  of  origin  through 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM  225 

proliferation  and  migration  of  the  endotheiial  elements.  This  method,  of 
course,  would  demonstrate  vessels  only  so  far  as  the  lumina  are  continuous. 
Solid  cords  of  cells  which  extend  beyond  the  field  of  injection  are  interpreted 
as  cords  of  endotheiial  cells  which  subsequently  acquire  lumina  and  become 
capillary  tubes.  If  this  theory  is  correct  then  the  vascularization  of  the 
area  pellucida  and  of  the  embryonic  body  would  be  effected  through  true 
outgrowths  of  the  original  endothelium  of  the  opaque  area.  Possible 
exceptions  to  this,  as  noted  above,  are  the  rudiments  of  the  heart,  the  aorta 
and  the  cardinal  veins  which  arise  in  situ  as  do  the  first  vascular  rudiments. 
Observations  upon  growing  vessels  in  living  embryos,  in  which  strands 
of  cells  were  seen  to  extend  from  the  endothelium  already  present,  have 
also  been  accepted  as  evidence  in  favor  of  this  view. 

The  evidence  afforded  by  injected  specimens  has  been  attacked  by  those 
who  believe  in  the  in  situ  origin  of  vessels,  on  the  ground  that  the  injection 
shows  only  vessels  with  continuous  lumina  and  does  not  prove  the  non- 
existence  of  isolated  vascular  rudiments  beyond  the  field  of  injection.  It  is 
claimed  that  the  vascular  field  becomes  more  extensive  through  the  gradual 
addition  of  such  isolated  spaces  to  the  channels  already  continuous,  in  the 
same  manner  that  the  primitive  blood  spaces  unite  to  form  a  network,  and 
the  claim  is  supported  by  demonstration  of  these  spaces  in  the  mesenchymal 
tissue  with  every  gradation  between  the  bordering  flattened  cells  (endo- 
thelium) and  the  branching  irregular  mesenchymal  cells.  The  actual 
formation  of  intercellular  spaces  with  flat  bordering  cells  and  their  union 
with  vascular  channels  have  been  observed  in  the  living  chick  blastoderm. 
Experimental  evidence  has  also  been  brought  to  bear  in  favor  of  the  view 
that  vessels  arise  in  situ.  The  area  opaca  was  entirely  removed  from  the 
chick  blastoderm  before  any  vascular  rudiments  had  appeared  in  the  area 
pellucida  and  the  blastoderm  was  then  allowed  to  develop  further;  it  was 
found  that  vascular  rudiments  appeared  both  in  the  area  pellucida  and 
embryonic  body  with  practically  the  same  disposition  as  in  the  normal 
embryo. 

The  concept  that  the  vascular  channels  are  structural  expressions  of  the 
functional  necessity  of  carrying  nutritive  materials  to  the  tissues  and  waste 
products  away  from  them  leads  to  consideration  of  such  factors  as  may  be 
involved  in  the  formation  of  vessels;  that  is,  factors  that  would  cause  plastic 
cells,  like  those  of  the  mesenchyme  in  which  the  earliest  and  simplest  vessels 
appear,  to  change  in  character  and  rearrange  themselves  to  form  capillary 
tubes.  In  a  mass  of  mesenchymal  tissue,  in  which  there  is  a  resemblance 
to  a  sponge  with  the  cellular  elements  representing  the  parenchyma  of  the 
sponge  and  the  intercellular  tissue  spaces  the  interstices,  the  products  of 
cell  activity  naturally  accumulate  in  the  intercellular  spaces.  Incident 


226  TEXT-BOOK  OF  EMBRYOLOGY 

to  this  accumulation,  pressure  would  be  exerted  upon  the  cells  bordering 
the  spaces.  Seeking  outlet  from  the  confines  of  the  spaces,  the  waste 
products  would  move,  or  now,  and  cause  friction  against  the  cells  past 
which  they  flow.  Similarly,  pressure  and  friction  would  result  from  the 
movement  of  nutritive  materials  to  and  through  the  tissue.  The  plastic 
mesenchymal  cells,  reacting  to  these  mechanical  influences,  would  tend  to 
become  flat,  and  the  continued  operation  of  the  factors  would  result  in  a 
smooth-walled  tube  in  which  the  movement  of  fluid  is  greatly  facilitated. 

The  reaction  of  the  irregular  mesenchymal  cells  to  the  mechanical  in- 
fluences of  pressure  and  friction  is,  of  course,  the  crux  of  the  question.  It 
has  been  shown  experimentally  that  cells  of  this  type  do  react  to  mechanical 
stimuli.  Smooth  non-irritating  foreign  bodies  have  been  imbedded  in  the 
loose  connective  tissue  of  an  animal  and  the  cells  in  contact  therewith  be- 
came flat  and  formed  a  mosaic  apparently  identical  with  simple  squamous 
epithelium  or  endothelium.  In  the  growth  of  mesenchymal  tissue  outside 
of  the  body  (in  vitro)  it  has  been  observed  that  the  cells  flatten  against 
foreign  substances  which  may  be  present. 

In  the  embryo  it  has  been  observed  that  where  blood  vessels  disappear, 
which  they  do  in  certain  regions,  the  endothelium  does  not  degenerate  but 
that  the  cells  assume  irregular  branching  forms.  This  would  indicate  that 
endothelium  comprises  merely  modified  mesenchymal  cells  and  that  upon 
removal  of  the  factors  incident  to  the  pressure  and  friction  of  blood  flow 
the  cells  reassume  the  indifferent  character  of  mesenchyme,  thus  reverting 
to  the  mesenchymal  type.  It  militates,  therefore,  against  the  view  that 
endothelium  is  a  specific  tissue. 

It  is  generally  recognized,  whether  or  not  the  endothelium  originates 
in  situ,  that  a  capillary  network  precedes  the  formation  of  larger  vessels. 
For  instance,  the  vitelline  plexus  of  capillaries  (p.  217)  antedates  any  of  the 
larger  vitelline  vessels  which  later  carry  blood  to  and  from  the  embryo. 
The  establishment  of  vascular  trunks  in  this  plexus  of  small  vessels  seems  to 
be  dependent  upon  the  same  mechanical  factors  that  were  considered  as 
operative  in  the  origin  of  vessels;  viz.:  pressure  and  friction.  If  the  volume 
of  blood  that  flows  through  a  given  capillary  network  at  a  given  rate  is  in- 
creased the  flow  will  naturally  follow  the  channels  that  offer  the  least  re- 
sistance, and  these  channels  will  increase  in  size  sufficiently  to  accommodate 
the  greater  volume.  A  few  channels,  or  perhaps  even  only  one,  will  form  the 
most  direct  course,  and  the  angles  in  the  course  will  be  still  further  reduced 
as  the  blood  stream  impinges  upon  the  walls  of  the  vessels.  In  this  manner 
a  large  vessel,  or  main  vascular  trunk,  is  established  and  the  remaining 
smaller  vessels  constitute  its  branches  or  tributaries.  A  rather  crude  analogy 
would  be  the  draining  of  a  swamp  in  which  a  small  rivulet,  once  gaining 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM  227 

slight  supremacy  over  its  fellows,  would  gradually  cut  its  way  deeper  into 
the  soil  and  pursue  a  straighter  course,  with  the  result  that  the  other  rivulets 
would  flow  into  it  as  the  main  channel. 

The  concept  that  the  main  vascular  trunks  are  preceded  by  a  capillary 
plexus,  out  of  which  they  develop  in  response  to  certain  mechanical  stimuli, 
offers  a  simple  explanation  of  the  numerous  variations  found  in  the  vascular 
system.  In  the  incipient  stages  of  the  larger  vessels  but  slight  influences, 
due  to  variations  in  the  development  of  surrounding  structures,  would  be 
sufficient  to  deflect  their  courses  and  cause  them  to  occupy  positions  which 
do  not  accord  with  the  normal.  So  far  as  the  thickened  walls  of  the  larger 
vascular  channels  are  concerned,  they  may  be  regarded  as  structural  adapta- 
tions to  the  functions  they  perform.  For  example,  the  large  amount  of 
elastic  tissue  in  the  wall  of  the  aorta  and  other  large  arteries  tends  to  main- 
tain a  uniform  diameter  in  these  vessels  against  the  force  exerted  by  the 
blood  expelled  from  the  heart  at  each  contraction. 

The  Heart. — The  heart  has  a  peculiar  origin  in  that  it  arises  as  two  sep- 
arate parts  or  anlagen  which  unite  secondarily.  In  the  chick,  for  example, 
it  appears  during  the  first  day  of  incubation,  at  a  time  when  the  germ  layers 
are  still  flat.  The  coelom  in  the  cephalic  region  becomes  dilated  to  form  the 
so-called  primitive  pericardial  cavity  (parietal  cavity),  and  at  the  same  time 
a  space  appears  on  each  side,  not  far  from  the  medial  line,  in  the  mesodermal 
layer  of  the  splanchnopleure  (Fig.  203) .  These  spaces  at  first  are  filled  with 
a  gelatinous  substance  in  which  lie  a  few  isolated  cells.  These  cells  then 
take  on  the  appearance  of  endothelium  and  line  the  cavities,  and  the  meso- 
thelium  in  this  vicinity  is  changed  into  a  distinct,  thickened  layer  of  cells. 
Now  by  a  bending  ventrally  of  the  splanchnopleure  the  cavities  or  vessels 
are  carried  toward  the  midventral  line  (Fig.  203).  The  bending  continues 
until  the  entoderm  of  each  side  meets  and  fuses  with  that  of  the  opposite 
side,  thus  closing  in  a  flat  cavity — the  fore-gut.  The  entoderm  ventral 
to  the  cavity  breaks  away  and  allows  the  medial  walls  of  the  two  endothelial 
tubes  to  come  in  contact.  These  walls  then  break  away  and  the  tubes  are 
united  in  the  midventral  line  to  form  a  single  tube  (Fig.  203),  which  extends 
longitudinally  for  some  distance  in  the  cervical  region  of  the  embryo.  The 
mesothelial  layers  of  opposite  sides  meet  dorsal  and  ventral  to  the  endo- 
thelial tube,  forming  the  dorsal  and  ventral  mesocardium  (Fig.  203).  In 
the  meantime  the  cephalic  end  of  the  tube  has  united  with  the  arterial  system, 
and  the  caudal  end  with  the  venous  system ;  and  in  a  short  time  the  dorsal 
and  ventral  mesocardia  disappear  and  leave  the  heart  suspended  by  its 
two  ends  in  the  primitive  pericardial  cavity.  The  conditions  at  this  point 
may  be  summarized  thus:  The  heart  is  a  double-walled  tube — the  inner  wall 
composed  of  endothelium  and  destined  to  become  the  endocardium,  the 


228 


TEXT-BOOK   OF  EMBRYOLOGY 


outer  wall  of  a  thicker  mesothelial  layer  and  destined  to  become  the  myo- 
cardium— the  two  walls  separated  by  a  considerable  space.  The  organ 
hangs,  as  it  were,  in  the  primitive  pericardial  cavity  (ccelom),  connected 


Dors,  ryesocardiuy 
sotr/  elluiy) 


Priry, 

fieri  ca.  ret,. 

Cavity 


FIG.  203. — Diagrams  showing  the  two  anlagen  of  the  heart  and  their  union  to  form  a  single 
structure;  made  from  camera  lucida  tracings  of  transverse  sections  of  chick  embryos. 
In  C  the  ventral  mesocardium  has  disappeared  (see  text). 

at  its  cephalic  end  with  the  ventral  aortic  trunk  and  at  its  caudal  end  with 
the  omphalomesenteric  veins. 

In  all  Mammals  thus  far  studied  the  principle  of  development  in  the 
earlier  stages  is  essentially  the  same  as  in  the  chick.  The  double  origin 
of  the  heart  is  even  more  marked  because  of  the  relatively  late  closure  of 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


229 


the  fore-gut.     There  are  no  observations  on  the  origin  of  the  heart  in  human 
embryos,  but  it  is  reasonable  to  assume  that  it  has  the  same  double  origin 


Dorsal  aortic  root 


Gut  (pharynx) 


•Pericardial 
cavity  (ccelom) 

Endocardium 
(endothelium) 


Myocardium 


FIG.  204. — Transverse  section  of  a  human  embryo  of  2.69  mm.     von  Spee,  Kollmann's  Atlas. 


Oral  fossa — 

Ventral  aortic, 

trunk"  " 


Ventricle 4 


Ant.  cardinal  vein 
Duct  of  Cuvier 
Umbilical  vein 


Ventricle 

Atrium 

Diaphragm 

Duct  of  Cuvier 

Liver 

Duct  of  liver 


FIG.  205. — Ventral  view  of  reconstruction  of  human  embryo  of  2.15  mm.     His. 

The  ventral  body  wall  has  been  removed.     The  vessels  (in  black)  at  the  sides  of  the  duct 

of  the  liver  are  the  omphalomesenteric  veins. 

as  in  other  Mammals,  although  in  embryos  of  2  to  3  mm.  the  organ  has 
already  become  a  single  tube  (Figs.  204  and  205).  At  this  stage  the  tube  is 
somewhat  coiled. 


230 


TEXT-BOOK  OF  EMBRYOLOGY 


While  the  double  origin  of  the  heart  is  characteristic  of  all  amniotic  Vertebrates 
(Reptiles,  Birds,  Mammals),  in  all  the  lower  forms  the  organ  arises  as  a  single  anlage.  In 
the  region  of  the  fore-gut  the  two  halves  of  the  coelom  are  separated  by  a  ventral  mesentery 
which  extends  from  the  gut  to  the  ventral  body  wall,  and  which  is  composed  of  two  layers 
of  mesothelium  with  a  small  amount  of  mesenchyme  between  them.  In  the  mesenchyme 
a  cavity  appears  and  is  lined  by  a  single  layer  of  flat  (endothelial)  cells.  This  cavity 
extends  longitudinally  for  some  distance  in  the  cervical  region  and  with  its  endothelial 
and  mesothelial  walls  constitutes  the  simple  cylindrical  heart.  On  the  dorsal  side  it  is 
connected  with  the  gut  by  a  portion  of  the  mesentery  which  is  called  the  dorsal  meso- 
cardium;  on  the  ventral  side  it  is  connected  with  the  ventral  body  wall  by  the  ventral 
mesocardium  (Fig.  206).  Thus  the  heart  is  primarily  a  single  structure.  The  difference 
between  the  two  types  of  development  is  not  a  fundamental  one  but  simply  depends  upon 
the  difference  in  the  germ  layers.  In  the  lower  forms  the  germ  layers  are  closed  in  ven- 


Entoderm 
Mesoderm  (visceral) 


Heart 

Pericard.  cavity 
(ccelom) 


Dorsal  mesocardium 

Endothelium 
Mesoderm  (parietal) 
Ventral  mesocardium 
Ectoderm 


FIG.  206. — Ventral  part  of  transverse  section  through  the  heart  region  of  Salamandra 
maculosa  embryo  with  4  branchial  arches.     RabL 

trally  from  the  beginning,  and  the  heart  appears  in  a  medial  position.  In  the  higher 
forms  the  germ  layers  for  a  time  remain  spread  out  upon  the  surface  of  the  yolk  or  yolk 
sac,  and  the  heart  begins  to  develop  before  they  close  in  on  the  ventral  side  of  the  embryo. 
Consequently  the  heart  arises  in  two  parts  which  are  carried  ventrally  by  the  germ  layers 
and  unite  secondarily. 

The  further  development  of  the  heart  consists  of  various  changes  in  the 
shape  of  the  tube  and  in  the  structure  of  its  walls.  At  the  same  time  the  dila- 
tation of  the  coelom  (primitive  pericardial  cavity)  in  the  cervical  region  is  of 
importance  in  affording  room  for  the  heart  to  grow.  In  the  chick,  for  ex- 
ample, the  tube  begins,  toward  the  end  of  the  first  day  of  incubation,  to 
bend  to  the  right;  during  the  second  day  it  continues  to  bend  and  assumes 
an  irregular  S-shape.  This  bending  process  has  not  been  observed  in 
human  embryos,  but  other  Mammals  show  the  same  process  as  the  chick. 
In  a  human  embryo  of  2.15  mm.  the  S-shaped  heart  is  present  (Fig.  205). 
The  venous  end,  into  which  the  omphalomesenteric  veins  open,  is  situated 
somewhat  to  the  left,  extends  cranially  a  short  distance  and  then  passes 
over  into  the  ventricular  portion.  The  latter  turns  ventrally  and  extends 
obliquely  across  to  the  right  side,  then  bends  dorsally  and  cranially  to  join 
the  aortic  bulb  which  in  turn  joins  the  ventral  aortic  trunk  in  the  medial 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM  231 

line.  The  endothelial  tube,  which  is  still  separated  from  the  muscular  wall 
by  a  considerable  space,  becomes  somewhat  constricted  at  its  junction  with 
the  aortic  bulb  to  form  the  so-called  f return  Halleri.  During  these  changes 
the  heart  as  a  whole  increases  in  diameter,  especially  the  ventricular  portion. 
Gradually  the  venous  end  of  the  heart  moves  cranially  and  in  embryos  of 


Vent,  aortic  tmnlr 


FIG.  207. — Ventral  view  heart  of  human  embryo  of  4.2  mm.     His. 
The  atria  are  hidden  behind  the  ventricular  portion. 

4.2  mm.  lies  in  the  same  transverse  plane  as  the  ventricular  portion.  The 
latter  lies  transversely  across  the  body  (Fig.  207).  At  the  same  time  two 
evaginations  appear  on  the  venous  end,  which  represent  the  anlagen  of  the 
atria.  In  embryos  of  about  5  mm.  further  changes  have  occurred,  which  are 
represented  in  Fig.  208.  The  two  atrial  anlagen  are  larger  than  in  the 


Right  atrium  [M  .:    JH          "^KSfc*  Left  atrium 


Right  ventricle    §'({.'  •  Left  ventricle 


Interventricular  furrow 
FIG.  208. — Ventral  view  of  heart  of  human  embryo  of  5  mm.     His. 

preceding  stage  and  surround,  to  a  certain  extent,  the  proximal  end  of  the 
aortic  trunk.  As  they  enlarge  still  more  in  later  stages,  they  come  in  con- 
tact, their  medial  walls  almost  entirely  disappear,  and  they  form  a  single 
chamber.  The  ventricular  portion  of  the  heart  becomes  separated  into  a 
right  and  a  left  part  by  the  interventricular  furrow  (Fig.  208) ;  the  right  part 


232 


TEXT-BOOK   OF  EMBRYOLOGY 


is  the  anlage  of  the  right  ventricle,  the  left  part,  of  the  left  ventricle.  At  the 
same  time  the  atrial  portion  has  moved  still  farther  cranially  so  that  it  lies 
to  the  cranial  side  of  the  ventricular  portion.  The  venous  and  arterial 
ends  of  the  heart  have  thus  reversed  their  original  relative  positions.  At 
this  point  it  should  be  noted  that  the  atrial  end  of  the  heart  is  connected 
with  the  large  venous  trunk  formed  by  the  union  of  the  omphalomesenteric 
veins  and  the  ducts  of  Cuvier — the  sinus  venosus. 

During  the  changes  in  the  heart  as  a  whole,  certain  changes  also  occur  in 
the  endothelial  and  muscular  walls.  The  walls  of  the  atria  are  composed 
of  compact  plates  of  muscle  with  the  endothelium  closely  investing  the  inner 
surface.  The  walls  of  the  ventricular  portion,  on  the  other  hand,  become 
thicker  and  are  composed  of  an  outer  compact  layer  of  muscle  and  an  inner 
layer  made  up  of  trabeculcc  which  are  closely  invested  by  the  endothelium. 


Septum  spurium 

Atrial  septum 
(septum  superius) 

Opening  of  sinus  venosus 


Right  atrium 
Left  atrium 
Atrio-ventricular  canal 


Right  ventricle 
Ventricular  septum 
Left  ventricle 


FIG.  209. — Dorsal  half  of  heart  (seen  from  ventral  side)  of  a  human  embryo  of  10  mm.     His. 


Everywhere  the  endothelium  is  closely  applied  to  the  inner  surface  of  the 
myocardium,  the  space  which  originally  existed  between  the  endothelium 
and  mesothelium  being  obliterated. 

The  embryonic  heart  in  Mammals  in  the  earlier  stages  resembles  that  of  the  adult  in 
the  lower  Vertebrates  (Fishes).  The  atrial  portion  receives  the  blood  from  the  body  veins 
and  conveys  it  to  the  ventricular  portion  which  in  turn  sends  it  out  through  the  arteries 
to  the  body.  The  circulation  is  a  single  one.  This  condition  changes  during  the  fcetal 
life  of  Mammals  with  the  development  of  the  lungs.  The  same  transition  occurs  in  the 
ascending  scale  of  development  in  the  vertebrate  series  in  those  forms  in  which  gill  breath- 
ing is  replaced  by  lung  breathing.  The  change  consists  of  a  division  of  the  heart  and 
circulation,  so  that  the  single  circulation  becomes  a  double  circulation.  In  other  words, 
the  heart  is  so  divided  that  the  lung  (pulmonary)  circulation  is  separated  from  the 
general  circulation  of  the  body.  This  division  first  appears  in  the  Dipnoi  (Lung  Fishes) 
and  Amphibians  in  which  gill  breathing  stops  and  lung  breathing  begins,  although  here 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


233 


the  division  is  not  complete.      In  Reptiles  the  division  is  complete  except  for  a  small 
direct  communication  between  the  ventricles. 

Fig.  209  represents  the  dorsal  half  of  the  heart  at  a  stage  when  all  the 
chambers  are  in  open  communication,  and  shows  the  conditions  in  a  single 
circulation  but  with  the  beginning  of  a  separation.  The  atria  are  rather 
thin- walled  chambers,  the  ventricles  have  relatively  thick  walls.  Between 
the  atrial  and  ventricular  portion  is  a  canal — the  atrio-ventricular  canal — 
which  affords  a  free  passage  for  the  blood.  From  the  cephalic  side  of  the 
atrial  portion  a  ridge  projects  into  the  cavity.  This  ridge  represents  a 
remnant  of  the  original  medial  walls  of  the  two  atria  and  marks  the  begin- 
ning of  the  future  atrial  septum.  The  opening  of  the  sinus  venosus  is  seen 
on  the  dorsal  wall  of  the  right  atrium.  Primarily  both  atria  communicated 


Septum  superius  •"•• 
Sinus  venosus   — 


Valvulse  venossc 
Right  atrium   -- 


Right  ventricle /„ 

Ventricular  septum  . 


FIG.  210. — Dorsal  half  of  heart  showing  chambers  and  septa. 

Modified  from  Born. 


Foramen  ovale 

—  Atrial  septum 

•  Left  atrium 

—  Atrio-ventricular  valves 

_  Atrio-ventricular  canals 
Left  ventricle 

(Semidiagrammatic.) 


directly  with  the  sinus  venosus,but  in  the  course  of  development  the  open- 
ing of  the  latter  migrated  to  the  right  and  at  this  stage  is  found  in  the  wall 
of  the  right  atrium.  The  opening  is  guarded,  as  it  were,  by  a  lateral  and  a 
medial  fold  the  significance  of  which  will  be  described  later.  The  vetricular 
portion  also  shows  a  ridge  projecting  from  the  caudal  side,  which  corresponds 
to  the  interventricular  groove  and  represents  the  beginning  of  the  ventricular 
septum. 

The  Septa. — The  further  changes  are  largely  concerned  with  the  separa- 
tion of  the  heart  into  right  and  left  sides,  and  with  the  development  of  the 
valves.  The  atria  become  separated  by  the  further  growth  on  the  cephalic 
side,  of  the  ridge  which  has  already  been  mentioned  and  which  is  known  as 
the  septum  superius  (Figs.  209  and  210).  This  septum  grows  across  the 
cavity  of  the  atria  until  it  almost  reaches  the  atrio-ventricular  canal,  form- 
ing the  septum  atriorum.  A  portion  of  the  septum  then  breaks  away,  leav- 
ing the  two  atria  still  in  communication.  This  secondary  opening  is  the 


234 


TEXT-BOOK   OF   EMBRYOLOGY 


foramen  ovale  which  persists  throughout  foetal  life,  but  closes  soon  after 
birth.     The  atrio-ventricular  canal  also  becomes  divided  into  two  passages 


Sinus  venosus 
Left  valvula  venosa 
Right  valvula  venosa 

Right  ventricle  ~~! 


Right  atrio- 
ventricular  canal 


Right  ventricle 


Atrial  septum 

Pulmonary  vein 


Left  atrium 


Left  atrio- 
ventricular  canal 


Left  ventricle 


Interventricular  furrow  Ventricular  septum 

FIG.  211. — Dorsal  half  of  heart  (ventral  view)  of  rabbit  embryo  of  5.8  mm.     Born. 

by  a  ridge  from  the  dorsal  w.all  and  one  from  the  ventral  wall  uniting  with 
each  other  and  finally  with  the  septum  atriorum  (Fig.  210).  Thus  the  two 
atria  would  be  completely  separated  if  it  were  not  for  the  foramen  ovale. 


Aorta 


Aortic  septum 


Interventricular  opening .;/_ 


Right  atrio-ventricu- 
lar orifice 


Right  ventricle 
Ventricular  septum 


Pulmonary  artery 


Aorta 


Left  atrio-ventricular  orifice 


-  Left  ventricle 


FIG.  212. — Ventricles  and  proximal  ends  of  aorta  and  pulmonary  artery  of  a  7.5  mm.   human 
embryo.    Lower  walls  of  ventricles  have  been  removed.     Kollmann's  Atlas. 

During  the  separation  of  the  atria,  a  division  of  the  ventricular  portion 
of  the  heart  also  occurs.     On  the  caudal  side  of  the  ventricular  portion  a 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM  235 

septum  appears  and  gradually  grows  across  the  cavity  forming  the  septum 
ventriculorum  (Figs.  209  and  210).  This  septum  is  situated  nearer  the  right 
side  and  is  indicated  on  the  outer  surface  by  a  groove  which  becomes  the 
sulcus  longitudinalis  anterior  and  posterior.  The  dorsal  edge  of  this  septum 
finally  fuses  with  the  septum  dividing  the  atrio-ventricular  canal,  but  for  a 
time  its  ventral  edge  remains  free,  leaving  an  opening  between  the  two 
ventricles  (Figs.  211  and  212). 

This  opening  then  becomes  closed  in  connection  with  the  division  of  the 
aortic  bulb  and  ventral  aortic  trunk.  On  the  inner  surface  of  the  aortic 
trunk,  at  a  point  where  the  branches  which  form  the  pulmonary  arteries 
arise,  two  ridges  appear,  grow  across  the  lumen  and  fuse  with  each  other, 
thus  dividing  the  vessel  into  two  channels.  This  partition — the  septum 
aorticum  (Fig.  213) — gradually  grows  toward  the  heart  through  the  aortic 
bulb  and  finally  unites  with  the  ventral  edge  of  the  ventricular  septum,  thus 
closing  the  opening  between  the  two  ventricles.  Corresponding  with  the 


FIG.  213. — Diagrams  representing  the  division  of  the  ventral  aortic  trunk  into  aorta  and 
pulmonary  artery-  and  the  development  of  the  semilunar  valves.     Hochstetter. 

edges  of  the  septum  aorticum,  a  groove  appears  on  each  side  of  the  aortic 
trunk  and  gradually  grows  deeper  and  extends  toward  the  heart,  until  finally 
the  trunk  and  aortic  bulb  are  split  longitudinally  into  two  distinct  vessels, 
one  of  which  is  connected  with  the  right  ventricle  and  becomes  the  pulmonary 
artery,  the  other  with  the  left  ventricle  and  becomes  the  proximal  part  of  the 
aortic  arch  (Fig.  212).  The  result  of  the  formation  of  these  various  septa  is 
the  division  of  the  entire  heart  into  two  sides.  The  atrium  and  ventricle 
of  each  side  are  in  communication  through  the  atrio-ventricular  foramen,  the 
two  sides  are  in  communication  only  by  the  foramen  ovale  which  is  but  a 
temporary  opening. 

After  the  opening  of  the  sinus  venosus  is  shifted  to  the  right  atrium,  the 
left  atrium  for  a  short  period  has  no  vessels  opening  into  it.  As  soon,  how- 
ever, as  the  pulmonary  veins  develop,  they  form  a  permanent  union  with  the 
left  atrium  (Fig.  211).  At  first  two  veins  arise  from  each  lung,  which  unite 
to  form  a  single  vessel  on  each  side;  the  two  single  vessels  then  unite  to  form 
a  common  trunk  which  opens  into  the  left  atrium  on  the  cephalic  side.  As 


236  TEXT-BOOK   OF  EMBRYOLOGY 

development  proceeds,  the  wall  of  the  single  trunk  is  gradually  absorbed  in 
the  wall  of  the  atrium,  until  the  single  vessel  from  each  side  opens  separately. 
Absorption  continuing,  all  four  veins,  two  from  each  lung  finally  open 
separately.  This  is  the  condition  usually  found  in  the  adult.  A  partial 
failure  in  the  absorption  may  leave  one,  two,  or  three  vessels  opening  into 
the  atrium.  Such  variations  are  not  infrequently  met  with  in  the  pulmonary 
veins. 

The  Valves. — If  all  the  passageways  between  the  different  chambers  of 
the  heart  and  the  large  vascular  trunks  were  to  remain  free  and  clear,  there 
would  be  nothing  to  prevent  the  blood  from  flowing  contrary  to  its  proper 
course.  Consequently  five  sets  of  valves  develop  in  relation  to  these  orifices, 
and  are  so  arranged  that  they  direct  the  blood  in  a  certain  definite  direction. 
These  appear  (a)  at  the  openings  of  the  large  venous  trunks  into  the  right 
atrium,  (b)  at  the  opening  between  the  right  atrium  and  right  ventricle, 
(c)  at  the  opening  between  the  left  atrium  and  left  ventricle,  (d)  at  the 
opening  between  right  ventricle  and  pulmonary  artery  and  (e)  at  the  open- 
ing between  the  left  ventricle  and  aorta.  No  valves  develop  at  the  openings 
of  the  pulmonary  veins  into  the  left  atrium. 

(a)  The  sinus  venosus  (which  is  formed  by  the  union  of  the  large  body 
veins)  opens  into  the  right  atrium  on  its  cranial  side,  as  has  already  been 
mentioned  (p.  232).  By  a  process  of  absorption,  similar  to  that  in  the  case 
of  the  pulmonary  veins,  the  wall  of  the  sinus  is  taken  up  into  the  wall  of  the 
atrium.  The  result  is  that  the  vena  cava  superior,  vena  cava  inferior,  and 
sinus  coronarius  (a  remnant  of  the  left  duct  of  Cuvier)  open  separately  into 
the  atrium.  As  the  sinus  is  absorbed,  its  wall  forms  two  ridges  on  the 
inner  surface  of  the  atrium,  one  situated  at  the  right  of  the  opening  and  one 
at  the  left  (Figs.  210  and  211).  These  two  ridges — valvulcz  venosce — are 
united  at  their  cranial  ends  with  the  septum  spurium  (Fig.  209),  a  ridge 
projecting  from  the  cephalic  wall  of  the  atrium.  The  septum  spurium 
probably  has  a  tendency  to  draw  the  two  valves  together  and  prevent  the 
blood  from  flowing  back  into  the  veins.  The  left  valve  and  the  septum 
spurium  later  atrophy  to  a  certain  extent  and  probably  unite  with  the  septum 
atriorum  to  form  part  of  the  limbus  fosses  ovalis  (Vieussenii) .  The  right 
valve  is  the  larger  and  in  addition  to  its  assistance  in  preventing  a  backward 
flow  of  blood  into  the  veins,  it  also  serves  to  direct  the  flow  toward  the 
foramen  ovale.  As  the  veins  come  to  open  separately,  the  cephalic  part 
of  the  right  valve  disappears;  the  greater  part  of  the  remainder  becomes 
the  valvula  vence  cavcz  inferioris  (Eustachii)  and  during  foetal  life  directs  the 
blood  toward  the  foramen  ovale.  In  the  adult  it  becomes  a  structure  of 
variable  size.  A  small  part  of  the  remainder  of  the  right  valve  forms  the  val- 
vula sinus  coronarii  (Thebesii)  which  guards  the  opening  of  the  coronary  sinus. 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM  237 

(b)  and  (c)  The  valves  between  the  atrium  and  ventricle  on  each  side 
develop  for  the  most  part  from  the  walls  of  the  triangular  atrio-ventricular 
opening  (ostium  atrio-ventriculare) .  Elevations  or  folds  appear  on  the  rims 
of  the  openings  and  project  into  the  cavities  of  the  ventricles  where  they 
become  attached  to  the  muscle  trabeculas  of  the  ventricle  walls  (Figs.  214 
and  215).  On  the  right  side  three  of  these  folds  appear,  and  develop  into  the 
vahula  tricuspidalis  which  guards  the  right  atrio-ventricular  orifice.  On 
the  left  side  only  two  folds  appear,  and  these  become  the  valvula  biscuspidalis 
(mitralis)  which  guards  the  left  atrio-ventricular  orifice.  These  valves, 
which  are  at  first  muscular,  soon  change  into  dense  connective  tissue.  The 
muscle  trabeculae  to  which  they  are  attached  also  undergo  marked  changes. 
Some  become  condensed  at  the  ends  which  are  attached  to  the  valves  into 
slender  tendinous  cords — the  chorda  tendinece,  while  at  their  opposite  ends 


Muscle  trabeculae 

Trabeculae  carneae 

FIG.  214. — Diagrams  representing  the  development  of  the  atrio-ventricular  valves,  chordae, 
tendinese,  and  papillary  muscles.     Gcgcnbaur. 

they  remain  muscular  as  the  Mm.  papillares;  others  remain  muscular  and 
lie  in  transverse  planes  in  the  ventricles,  or  fuse  with  the  more  compact 
part  of  the  muscular  wall,  or  form  irregular,  anastomosing  bands  and  con- 
stitute the  trabecula  carnea  (Fig.  214). 

(d)  and  (e)  The  valves  of  the  pulmonary  artery  and  aorta  develop  at  the 
point  where  originally  the  endothelial  tube  was  constricted  to  form  the 
f return  Halleri  (p.  231)  where  the  ventricular  portion  of  the  heart  joined 
the  aortic  bulb.  Before  the  aortic  trunk  and  bulb  are  divided  into  the  aortic 
arch  and  pulmonary  artery,  four  protuberances  appear  in  the  lumen  (Fig. 
213).  The  septum  aorticum  then  divides  the  two  which  are  opposite  so  that 
each  vessel  receives  three  (Fig.  213).  These  then  become  concave  on  the 
side  away  from  the  heart,  in  a  manner  which  has  not  been  fully  determined, 
and  at  the  same  time  enlarge  so  that  they  close  the  lumen.  Those  in  the 
pulmonary  artery  are  known  as  the  valvula  semilunares  arterice  pulmonalis, 
those  in  the  aorta  as  the  valvula  semilunares  aorta. 

Changes  after  Birth. — The  migratory  changes  of  the  heart  from  its  origi- 
nal position  in  the  cervical  region  to  its  final  position  in  the  thorax  will  be  con- 


238 


TEXT-BOOK  OF  EMBRYOLOGY 


sidered  in  connection  with  the  development  of  the  pericardium  (Chap.  XIV). 
With  the  exception  of  the  septum  atriorum,  the  heart  acquires  during  foetal 
life  practically  the  form  and  structure  characteristic  of  the  adult  (Fig. 
216).  So  long  as  the  individual  continues  to  grow,  the  heart,  generally 
speaking,  increases  in  size  accordingly.  This  increase  takes  place  by  in- 
tussusception in  the  endocardium  and  myocardium.  At  the  time  of  birth 
the  two  atria  are  in  communication  through  the  foramen  ovale  which  is 


Dorsal  aortic  roots 


Amnion 


Upper  limb  bud 


Atrial  septum 

Right  atrium 

Right  atrio- 

ventricular 

(tricuspid)  valves 

Right  ventricle 


Pericardial  cavity 


Left  atrium 


Left  atrio- 
ventricular 
(bicuspid)  valves 


Left  ventricle 


FIG.  215. — Transverse  section  of  pig  embryo  of  14  mm.     Photograph. 

simply  an  orifice  in  the  atrial  septum  (Fig.  217).  Thus  the  blood  which  is 
brought  to  the  right  atrium  by  the  body  veins  is  allowed  to  pass  directly 
into  the  left  atrium,  thence  to  the  left  ventricle,  and  thence  is  forced  out  to 
the  body  again  through  the  aorta.  A  certain  amount  of  blood  also  passes 
from  the  right  atrium  into  the  right  ventricle  and  thence  into  the  pulmonary 
artery;  but  this  blood  does  not  enter  the  lungs  but  passes  directly  into  the 
aorta  through  the  ductus  arteriosus  (Fig.  216).  After  birth  the  lungs  begin 


THE  DEVELOPMENT  OF  THE  VASCULAR   SYSTEM 


239 


Innominate  artery 

Branches  of  right 
pulmonary  artery " 

Arch  of  aorta 
Pulmonary  artery 


Right  auricular  appendage-  -  -j-  ---  7 


•  Left  carotid  artery 
Left  subclavian  artery 

Ductus  arteriosus 


Branches  of  left 
pulmonary  artery 


— Left  auricular  appendage 


— --„-—  Left  ventricle 


Right  ventricle  i-_--\- -  - 


Descending  aorta 

FIG.  216.— Ventral  view  of  heart  of  foetus  at  term.     Kollmann's  Atlas. 


Sup.  vena  cava- 


Inf .  vena  cava 


Right  atrium- 


Right  ventricle  .-„  .  _ 


Inf.  vena  cava 


Left  ventricle 


FIG.  217.— Dorsal  half  of  foetal  heart.     Bumm,  Kollmann's  Atlas. 


240 


TEXT-BOOK   OF   EMBRYOLOGY 


to  function  and  the  placental  blood  is  cut  off,  so  that  the  right  atrium  receives 
venous  blood  only  and  the  left  arterial  blood  only.  If  the  foramen  ovale  were 
to  persist  it  would  allow  a  mingling  of  venous  and  arterial  blood.  Con- 
sequently the  foramen  ovale  closes  soon  after  birth  and  the  two  currents  of 
blood  are  completely  separated.  At  the  same  time  the  ductus  arteriosus 
atrophies  and  becomes  the  ligamentum  arteriosum.  Consequently  there  is 
no  direct  communication  between  the  pulmonary  artery  and  aorta. 

Certain  features  of  development  have  an  important  bearing  on  the  theories  regarding 
the  physiology  of  the  heart,  particularly  on  the  theory  that  the  heart  is  an  automatic 
organ.  Whether  the  theory  that  the  heart  beats  automatically,  i.e.,  independently  of 
stimuli  from  the  nervous  system,  is  true  or  not,  it  is  a  fact  that  in  the  embryo  it  begins  to 
beat  before  any  nerve  cells  appear  in  it  and  before  any  nerve  fibers  are  connected  with  it. 
At  least  no  technic  has  yet  been  devised  by  which  it  is  possible  to  demonstrate  nerve  cells 
in,  or  fibers  connected  with  it,  at  the  time  when  it  begins  to  perform  its  characteristic 
function.  And,  furthermore,  at  the  time  when  the  heart  begins  to  beat,  no  heart  muscle 
cells  are  developed.  This  last  fact  seems  to  indicate  an  inherent  contractility  in  the 
mesothelial  cells  which  form  the  anlage  of  the  myocardium. 

The  Arteries. — The  simplest  condition  of  the  arterial  system,  following 
the  establishment  of  the  vitelline  and  allantoic  circulation  (p.  220  and  p. 


Dors,  aortic  root 


— «    Dors,  aortic  root 


Vent,  aortic  root   '         ^^    ,  ^  /   ^  ,    ,^^_    ^ 

(Esophagus 

Vent,  aortic  trunk    ""  "^W  \      ^^ "    Trachea 

\ - - :  Pulmonary  artery 

FIG.  218. — From  reconstruction  of  aortic  arches  (i,  2,  3,  4,  6)  of  left  side  and  pharynx 

of  a  5  mm.  human  embryo.     Tandler. 

I-IV,  Inner  branchial  grooves. 

222),  is  as  follows:  The  single  ventral  aortic  trunk  is  given  off  from  the 
cephalic  end  of  the  heart.  This  is  a  short  vessel,  soon  dividing  into  the 
two  ventral  aortic  roots  which  pass  forward  beneath  the  pharynx  (Fig.  218). 
Each  ventral  aortic  root  gives  rise  to  branches  which  pass  dorsally,  one  in 
each  branchial  arch,  as  the  aortic  arches  to  unite  in  a  common  stem  along 
the  dorsal  wall  of  the  pharynx.  This  common  stem  is  the  dorsal  aortic 
root  (Fig.  218)  which  fuses  with  its  fellow  of  the  opposite  side  in  the  mid- 
dorsal  line  to  form  the  dorsal  aorta.  The  single  dorsal  aorta,  situated 
ventral  to  the  notochord,  extends  from  the  cervical  region  to  the  caudal 
end  of  the  embryo.  Somewhat  caudal  to  the  middle  of  the  embryo  a  branch 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


241 


of  the  aorta  passes  ventrally  through  the  mesentery  as  the  vitelline  artery 
which  enters  the  umbilical  cord  (Fig.  202).  Still  farther  caudally  the 
paired  umbilical  (allantoic)  arteries  are  given  off  from  the  aorta  and  pass 
out  into  the  umbilical  cord  (Fig.  202). 

The  conditions  which  exist  at  this  stage  in  the  region  of  the  aortic  arches" 
in  mammalian  embryos  are  indicative  of  the  conditions  which  persist  as  a' 
whole  or  in  part  throughout  life  in  the  lowest  Vertebrates.  The  changes' 
which  occur  in  Mammals,  however,  are  profound  and  the  adult  condition 
bears  no  resemblance  to  the  embryonic.  Yet  certain  features  in  the  adult 
are  intelligible  only  from  a  knowledge  of  their  development.  In  the  human  ( 

Vent,  aortic  roots 


Ventral  aortic  trunk 


Gubclavian  arteries 


Aorta 


FIG.  219. — Diagram  of  the  aortic  arches  of  a  Mammal.     Modified  from  Ilochstettcr. 


embryo  six  aortic  arches  appear  on  each  side.  The  first,  second,  third,  and 
fourth  pass  through  the  corresponding  branchial  arches.  The  fifth  arch, 
which  is  merely  a  loop  from  the  fourth,  seems  to  pass  through  the  fourth 
branchial  arch.  The  sixth  aortic  arch  passes  through  the  region  behind 
the  fourth  branchial.  All  these  arches  are  present  in  embryos  of  5  mm. 
(Fig.  218).  In  Fishes  and  larval  Amphibians,  where  the  branchial  arches 
develop  into  the  gills,  the  aortic  arches  are  broken  up  into  capillary  net- 
works which  ramify  in  the  gills,  and  the  ventral  aortic  root  becomes  the 
afferent  vessel,  the  dorsal  aortic  roots  the  efferent  vessels.  In  the  higher 
Vertebrates  and  in  man  the  aortic  arches  begin,  at  a  very  early  period,  to 


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TEXT-BOOK   OF  EMBRYOLOGY 


undergo  changes;  some  disappear  and  others  become  portions  of  the  large 
arterial  trunks  which  leave  the  heart.  In  connection  with  the  following 
description,  constant  reference  to  Figs.  219  and  220  will  assist  the  student  in 
understanding  the  changes. 

The  first  and  second  arches  soon  atrophy  and  disappear.  The  third 
arch  on  each  side  becomes  the  proximal  part  of  the  internal  carotid  artery, 
while  the  continuation  of  the  dorsal  aortic  root,  cranially  to  the  third  arch, 
becomes  its  more  distal  part.  The  continuation  of  the  ventral  aortic  root 
cranially  to  the  third  arch,  becomes  the  proximal  part  of  the  external  carotid 


Common  carotid  arteries 


Int.  carotid  artery  (right) 
Ext.  carotid  artery  (right)  • 


n  •, 

Int.  carotid  III 

Subclavian  IV 

V 

VI 

Innominate  artery 

Subclavian  artery  (right) 


Int.  carotid  artery  (left) 


Ext.  carotid  artery  (left) 


II 

III  Int.  carotid 
'  IV  Arch  of  aorta 
V 

VI  Ductus  arteriosus 


Pulmonary  artery 
Subclavian  artery  (left) 
Aorta 


FIG.  220. — Diagram  representing  the  changes  in  the  aortic  arches  of  a  Mammal. 
Compare  with  Fig.  219.     Modified  from  Hochstetter. 

artery,  while  the  portion  of  the  ventral  aortic  root  between  the  third  and 
fourth  arches  becomes  the  common  carotid  artery.  The  portion  of  the  dorsal 
aortic  root  between  the  third  and  fourth  arches  disappears.  The  fourth 
aortic  arch  on  the  left  side  enlarges  and  becomes  the  arch  of  the  aorta  (arcus 
aorta)  which  is  then  continued  caudally  through  the  left  dorsal  aortic  root 
into  the  dorsal  aorta.  On  the  right  side,  the  fourth  arch  becomes  the  proxi- 
mal part  of  the  Subclavian  artery.  Since  the  third,  fourth,  fifth,  and  sixth 
arches  really  leave  the  ventral  aortic  trunk  as  a  single  vessel,  it  will  be  seen 
that  these  changes  bring  it  about  that  the  common  carotid  and  subclavian 


THE   DEVELOPMENT  OF  THE  VASCULAR  SYSTEM  243 

on  the  right  side  arise  by  a  common  stem,  the  innominate  artery,  which  in 
turn  is  a  branch  of  the  arch  of  the  aorta.  On  the  left  side,  for  the  same 
reason,  the  common  carotid  is  a  branch  of  the  arch  of  the  aorta.  The  fifth 
aortic  arch  from  the  beginning  is  rudimentary  and  disappears  very  early. 
The  sixth  arch  on  each  side  undergoes  wide  changes.  A  branch  from  each 
enters  the  corresponding  lung.  On  the  right  side  the  portion  of  the  sixth 
arch  between  the  branch  which  enters  the  lung  and  the  dorsal  aortic  root 
disappears,  as  does  also  that  portion  of  the  right  dorsal  aortic  root  between 
the  subclavian  artery  and  the  original  bifurcation  of  the  dorsal  aorta.  On 
the  left  side,  however,  that  portion  of  the  sixth  arch  between  the  branch 
which  enters  the  lung  and  the  dorsal  aortic  root  persists  until  birth  as  the 
ductus  arleriosiis  (Botalli).  This  conveys  the  blood  from  the  right  ventricle 
to  the  aorta  until  the  lungs  become  functional  (Fig.  216);  it  then  atrophies 


Int.  carotid  artery 


Vertebral  artery 


Segmental  cervical  artery 


^' r —    Pulmonary  artery 

FIG.  221. — Diagram  cf  the  aortic  arches  (III,  IV,  VI)  and  segmented  cervical  arteries 
cf  a  10  mm.  human  embryo.    His. 

and  becomes  the  ligamentum  arteriosum.  In  the  meantime  the  septum 
aorticum  has  divided  the  original  ventral  aortic  trunk  into  two  vessels  (see 
P-  235)j  one  of  the  vessels  communicates  with  the  left  ventricle  and  is  the 
proximal  part  of  the  arch  of  the  aorta,  the  other  communicates  with  the  right 
ventricle  and  becomes  the  large  pulmonary  artery  (Fig.  212). 

In  human  embryos  of  10  mm.  the  dorsal  aortic  root  on  each  side  gives  off 
several  lateral  branches — the  segmental  cervical  vessels  (Fig.  221).  The 
first  of  these  (first  cervical,  suboccipital),  which  arises  nearly  opposite  the 
fourth  aortic  arch,  is  a  companion,  as  it  were,  to  the  hypoglossal  nerve,  and 
sends  a  branch  cranially  which  unites  with  its  fellow  of  the  opposite  side  in- 
side the  skull  to  form  the  basilar  artery.  The  basilar  artery  again  bifurcates 
and  each  branch  unites  with  the  corresponding  internal  carotid  by  means  of 
the  circulus  arteriosus  (Fig.  223).  The  other  segmental  cervical  vessels 
arise  from  the  aortic  root  at  intervals,  the  eighth  arising  near  the  point  of 


244 


TEXT-BOOK  OF  EMBRYOLOGY 


bifurcation  of  the  aorta.  In  a  short  time  a  longitudinal  anastomosis  appears 
between  these  segmental  arteries,  which  extends  as  far  as  the  seventh  (Fig. 
222).  The  proximal  ends  of  the  first  six  disappear,  and  the  longitudinal 


r.  carotid 
£xt  carotid 


-Sub.  inter- 
art. 


FIG.  222. — Diagram  illustrating  the  formation  of  the  vertebral  and  superior  intercostal  arteries. 
The  broken  lines  represent  the  portions  of  the  original  segmental  vessels  that  disappear. 
Modified  from  Hochstetter. 

vessel  forms  the  vertebral  artery  which  then  opens  into  the  aortic  root  through 
the  seventh  segmental  artery,  and  which  is  continued  cranially  as  the 
basilar  artery  (Fig.  223).  The  seventh  (it  is  held  by  some  to  be  the  sixth) 


Circulus  arteriosus 


Middle  cerebral 
artery 


Basilar  artery 
Int.  carotid  artery 


FIG.  223. — Brain  and  arteries  of  a  human  embrvo  of  o  mm.     Matt. 

segmental  artery  becomes  the  subclavian,  and  consequently  the  vertebral 
opens  into  the  subclavian,  as  in  the  adult  (Fig.  222).  But  it  should  be 
borne  in  mind  that  the  right  subclavian  artery  is  more  than  equivalent  to 
the  left,  since  the  proximal  part  of  the  former  is  made  up  of  the  fourth 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


245 


aortic  arch  and  a  part  of  the  aortic  root  (see  Figs.  219  and  220).  Further- 
more, changes  occur  in  the  position  of  the  heart  during  development,  which 
alter  the  relations  of  the  vessels.  The  heart  migrates  from  its  original 
position  in  the  cervical  region  into  the  thorax,  and  this  produces  an  elonga- 
tion of  the  carotid  arteries  and  an  apparent  shortening  of  the  arch  of  the 
aorta;  consequently  the  subclavian  artery  on  the  left  side  arises  relatively 
nearer  the  heart. 

The  arteries  of  the  brain  arise  as  branches  of  the  internal  carotid  and  circu- 
lus  arteriosus.  The  anterior  cerebral  artery  and  the  middle  cerebral  artery 
arise  primarily  from  a  common  stem  which  in  turn  is  a  branch  of  the  most 
cranial  part  of  the  internal  carotid  (Figs.  223  and  224).  The  posterior 
cerebral  artery  arises  as  a  branch  of  the  circulus  arteriosus  (Fig.  224). 


Post,  cerebral  vein 
(sup.  petrosal  sinus) 


irculus  arteriosus 
Transverse  sinus 

Basilar  artery 
Int.  jugular  vein 


Confluence  of  sinuses 

Inf.  sagittal  sinus 
Sup.  sagittal  sinus 
Post,  cerebral  artery 

Ant.  cerebral  artery 
Int.  carotid  artery 


FIG.  224. — Brain,  arteries  and  veins  of  a  human  embryo  of  23  mm.     Mali 

From  the  point  of  its  bifurcation  to  its  caudal  end  the  aorta  gives  off 
paired,  segmental  branches  which  accompany  the  segmental  nerves.  The 
last  (eighth)  cervical  branch  and  the  first  two  thoracic  branches  undergo 
longitudinal  anastomoses,  similar  to  those  between  the  first  seven  cervical, 
to  form  the  superior  intercostal  artery  (A.  intercostalis  suprema)  which  opens 
into  the  subclavian  (Fig.  222).  The  other  thoracic  branches  persist  as  the 
intercostal  arteries;  the  lumbar  branches  persist  as  the  lumbar  arteries.  At 
the  same  time  anastomoses  are  formed  between  the  distal  ends  of  the  inter- 
costal and  lumbar  arteries  in  the  ventro-lateral  region  of  the  body  wall, 
which  give  rise,  on  the  one  hand,  to  the  internal  mammary  artery  and,  on 
the  other  hand,  to  the  inferior  epigastric  artery.  Of  these  two  the  former 
opens  into  the  subclavian,  the  latter  into  the  external  iliac.  By  a  further 
anastomosis  the  distal  ends  of  the  internal  mammary  and  inferior  epigastric 
are  joined,  thus  forming  a  continuous  vessel  from  the  subclavian  to  the 
external  iliac  (Fig.  225).  It  is  interesting  to  note  that  while  originally  all 
the  lateral  branches  of  the  aorta  are  arranged  segmentally,  many  of  them 


246 


TEXT-BOOK  OF  EMBRYOLOGY 


lose  their  segmental  character  and  are  replaced  or  supplemented  by  longi- 
tudinal vessels. 

In  addition  to  the  dorsal  segmental  branches  of  the  aorta,  which  have 
been  described,  other  branches  develop  which  carry  blood  to  the  viscera. 
A  number  of  these,  or  possibly  all,  are  also  primarily  segmental  vessels, 
although  they  lose  every  trace  of  their  segmental  character  during  develop- 
ment. The  first  of  the  visceral  branches  to  appear  is  the  omphalomesenteric 
artery  which  arises  from  the  ventral  side  of  the  aorta  and  which  has  been 
mentioned  in  connection  with  the  vitelline  circulation.  Originally  it  passes 


Int.  mammary  artery 


Inf.  epigastric  artery 


Umbilical  artery 


Femoral  artery 


FIG.  225. — Diagram  of  human  embryo  of  13  mm.,  showing  the  mode  of  development 
of  the  internal  mammary  and  inferior  epigastric  arteries.     Mall. 

out  through  the  mesentery  and  follows  the  yolk  stalk  to  ramify  on  the  surface 
of  the  yolk  sac.  But  since  the  yolk  sac  is  of  slight  importance,  the  distal 
part  of  the  artery  soon  disappears,  while  the  proximal  part  becomes  the 
superior  mesenteric  artery  (Fig.  226) .  The  codiac  artery  arises  from  the  ventral 
side  of  the  aorta  a  short  distance  cranially  to  the  omphalomesenteric  (Fig. 
226)  and  gives  rise  in  turn  to  the  gastric,  hepatic  and  splenic  arteries.  The 
inferior  mesenteric  artery  also  arises  from  the  ventral  side  of  the  aorta  some 
distance  caudal  to  the  omphalomesenteric  (Fig.  226).  In  the  early  stages 
these  visceral  arteries  arise  relatively  much  farther  cranially  than  in  the 


THE  DEVELOPMENT  OF  THE   VASCULAR   SYSTEM 


247 


adult.     During  development  they  gradually  migrate  caudally  to  their  normal 
positions. 

Other  branches  of  the  aorta  develop  in  connection  with  the  urinary  and 
genital  organs.  Several  lateral  branches  supply  the  mesonephroi,  but  when 
the  latter  atrophy  and  disappear  the  vessels  also  disappear.  A  periaortic 
plexus  of  vessels,  with  many  branches  from  the  aorta,  supplies  the  develop- 
ing kidneys  until  these  organs  reach  their  definitive  position,  when  one  of 
the  branches  on  each  side  enlarges  to  become  the  renal  artery.  The  de- 
veloping genital  glands  are  likewise  supplied  by  several  branches  from  the 
aorta.  Later  the  majority  of  these  vessels  disappear,  one  pair  only  per- 
sisting as  the  internal  spermatic  arteries  which  differ  in  accordance  with  the 


Coeliac  artery 


Sup.  mesenteric 
(vitelline)  artery 


Umbilical  artery 


Aorta 


Duodenum 

Inf.  mesenteric  artery 
Int.  iliac  artery 


FIG.  226. — Diagram  of  the  visceral  arteries  in  a  human  embryo  of  12.5  mm.     Tandler. 
Numerals  indicate  segmental  arteries. 

sex  of  the  individual.  In  both  sexes  they  are  at  first  very  short;  in  the 
female,  as  the  ovaries  move  farther  into  the  pelvic  region,  they  become 
considerably  elongated  to  form  the  ovarian  arteries;  in  the  male,  with  the 
descent  of  the  testes,  they  become  very  much  elongated  to  form  the  testicular 
arteries. 

The  fifth  (or  fourth?)  pair  of  segmental  lumbar  arteries  primarily  gives 
rise  to  the  vessels  which  supply  the  lower  extremities,  viz.,  the  iliac  arteries. 
These  then  would  be  serially  homologous  to  the  subclavians.  But  certain 
changes  occur  in  this  region,  which  are  due  to  the  relations  of  the  umbilical 
arteries.  The  latter,  as  has  already  been  noted,  arise  as  paired  branches  of 
the  aorta  in  the  lumbar  region,  pass  ventrally  through  the  genital  cord 
(Chap.  XV)  and  then  follow  the  allantois  (urachus)  to  the  umbilical  cord. 


248  TEXT-BOOK  OF  EMBRYOLOGY 

During  foetal  life  they  carry  all  the  blood  that  passes  to  the  placenta.  At  an 
early  period  a  branch  from  each  iliac  artery  anastomoses  with  the  corre- 
sponding umbilical,  and  the  portion  of  the  umbilical  artery  between  the 
aorta  and  the  anastomosis  then  disappears.  This  makes  the  umbilical 
artery  a  branch  of  the  iliac;  and  the  blood  then  passes  from  the  aorta  into 
the  proximal  part  of  the  liiac  which  becomes  the  common  iliac  artery  of  the 
adult.  At  birth,  when  the  umbilical  cord  is  cut,  the  umbilical  arteries  no 
longer  carry  blood  to  the  placenta,  and  their  intraembryonic  portions, 
often  called  the  hypogastric  arteries,  persist  only  in  part;  their  proximal 
ends  persist  as  the  superior  vesical  arteries,  while  the  portions  which  accom- 
panied the  urachus  degenerate  to  form  the  lateral  umbilical  ligaments. 

So  far  as  a  complete  history  of  the  growth  of  the  arteries  of  the  extremities 
is  concerned,  knowledge  is  lacking.  The  facts  of  comparative  anatomy  and 
the  anomalies  which  occur  in  the  human  body  have  led  to  certain  conclusions 
which  have  been  largely  confirmed  by  embryological  observations;  but  much 
more  work  on  the  development  of  the  arteries  is  yet  necessary  to  complete 
their  history.  The  extremities  represent  outgrowths  from  several  segments 
of" the  body,  the  nerve  supply  is  derived  from  several  segments,  and  the 
limb  buds  are  likewise  primarily  supplied  by  plexuses  of  vessels  arising  from 
several  branches  of  the  aorta.  In  the  upper  extremity  the  subclavian,  which 
represents  the  seventh  cervical  branch  of  the  aortic  root,  is  the  single  vessel 
which  eventually  develops  out  of  the  original  plexus.  In  the  lower  extremity 
the  common  iliac,  which  represents  the  fifth  lumbar  branch  of  the  aorta, 
is  the  single  vessel  which  develops  out  of  the  plexus  supplying  the  lower 
limb  bud. 

In  the  upper  extremity  the  subclavian  grows  as  a  single  vessel  to  the  wrist 
and  then  divides  into  branches  corresponding  to  the  fingers.  In  the  forearm 
it  lies  between  the  radius  and  ulna.  In  a  short  time  a  branch  is  given  off 
just  distal  to  the  elbow  and  accompanies  the  median  nerve.  As  this  branch 
increases,  the  original  vessel  in  the  forearm  diminishes  to  form  the  -uolar 
interosseous  artery;  and  at  the  same  time  the  branch  unites  again  with  the 
lower  end  of  the  interosseous,  takes  up  the  digital  branches  and  becomes 
the  chief  vessel  of  the  forearm  at  this  stage,  forming  the  median  artery. 
Later,  however,  it  diminishes  in  size  as  another  vessel  develops,  the  ulnar 
artery,  which  arises  a  short  distance  proximal  to  the  origin  of  the  median  and, 
passing  along  the  ulnar  side  of  the  forearm,  unites  with  the  median  to  form 
the  superficial  volar  arch.  From  the  artery  of  the  arm,  which  is  called  the 
brachial  artery,  a  branch  develops  about  the  middle  and  extends  distally 
along  the  radial  side  of  the  forearm.  A  little  later  another  branch  grows  out 
from  the  brachial  just  proximally  to  the  origin  of  the  ulnar  and  extends  across 
to,  and  anastomoses  with,  the  first  branch.  Then  the  portion  of  the  first 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


249 


branch  between  its  point  of  origin  and  the  anastomosis  atrophies,  leaving 
only  a  small  vessel  which  goes  to  the  biceps  muscle.  The  second  branch 
and  the  remaining  part  of  the  first  branch  together  form  the  radial  artery 
(Fig.  227)  (McMurrich). 

In  the  lower  extremity  the  primary  artery  is  a  continuation  of  the  common 
iliac  which,  in  turn,  is  a  branch  of  the  aorta.  This  primary  vessel,  the  sciatic 
artery,  passes  distally  as  far  as  the  ankle.  Below  the  knee  it  gives  off  a  short 
branch  which  corresponds  to  the  proximal  part  of  the  anterior  tibial  artery. 
Just  above  the  ankle  it  gives  off  another  branch  which  corresponds  to  the 
distal  part  of  the  anterior  tibial.  As  will  be  seen,  these  two  parts  join  at  a 
later  period  to  form  a  continuous  vessel.  At  this  early  stage  the  external 


Brachial  artei 1" 


Superficial  radia*  artery- — •—  • 

Median  artery  — 
Interosseous  artery  — 


Ulnar  artery y 

A 


Brachial  artery 


B 


....  Median  artery 

--«  Interosseous  artery 
----  Ulnar  artery 


Radial  artery 


FIG.  227. — Diagrams  showing  (A)  an  early  and  (5)  a  late  stage  in  the  development 
of  the  arteries  of  the  upper  extremity.     McMurrich. 

iliac  artery  is  but  a  small  branch  of  the  common  iliac;  but  it  gradually  in- 
creases in  size,  extends  farther  distally  in  the  thigh  as  the  femoral  artery 
and  unites  with  the  sciatic  near  the  knee.  Just  proximal  to  its  union  with 
the  sciatic  it  gives  off  a  branch  which  extends  distally  along  the  inner  side 
of  the  leg  to  the  plantar  surface  of  the  foot,  where  it  gives  off  the  digital 
branches.  This  vessel  is  the  saphenous  artery  in  the  embryo,  and  disappears 
in  part  during  further  development.  From  this  time  on,  the  femoral  and  its 
direct  continuation,  the  popliteal,  increase  in  size;  and  at  the  same  time  the 
sciatic  loses  its  primary  connection  and  becomes  much  reduced  to  form  the 
inferior  gluteal  artery.  The  direct  continuation  of  the  sciatic  in  the  leg,  which 
is  now  the  direct  continuation  of  the  popliteal,  becomes  reduced  to  form  the 


250 


TEXT-BOOK  OF   EMBRYOLOGY 


peroneal  artery.  The  branch  of  the  original  sciatic,  which  was  given  off  just 
below  the  knee,  unites  with  the  branch  which  was  given  off  just  above  the 
ankle  to  form  a  continuous  vessel,  the  anterior  tibial  artery.  A  new  branch 
arises  from  the  proximal  portion  of  the  peroneal,  extends  down  the  back  of 
the  leg,  and  unites  with  the  distal  part  of  the  embryonic  saphenous  to 
form  the  posterior  tibial  artery.  The  proximal  part  of  the  saphenous  then 
atrophies,  leaving  but  one  of  the  small  genu  branches  of  the  popliteal  (Fig. 
228)  (McMurrich). 


~~  Sciatic  artery 
"Femoral  artery 


. 

I 

n 

\\ 

( 

\ 

4 

ors.  artery  of  foot  ^-'-  -11  -  - 

---I 

n 

I 

•  Popliteal  artery 


v Ant.  tibial  artery 

Peroneal  artery 

Post,  tibial  artery 


FIG.  228. — Diagrams  showing  three  stages  in  the  development  of  the  arteries 
of  the  lower  extremity.     McMurrich. 

The  Veins. — The  changes  which  occur  during  the  development  of  the 
venous  system  are  so  complicated,  and  in  some  cases  so  varied,  that  the  scope 
of  this  book  permits  only  a  brief  outline  of  the  growth  of  the  more  important 
of  the  venous  trunks. 

Corresponding  to  the  arterial  system,  the  first  veins  to  appear  are  the 
omphalomesenteric  veins.  These  vessels,  which  carry  blood  from  the  yolk  sac 
to  the  heart,  arise  in  the  area  vasculosa,  enter  the  embryonic  body  at  the  sides 
of  the  yolk  stalk,  pass  cranially  along  the  intestinal  tract,  and  join  the  caudal 
end  of  the  heart  (Figs.  198,  200,  202  and  231).  Next  in  point  of  time  to  ap- 
pear are  the  umbilical  veins  which  carry  back  to  the  heart  the  blood  which 
has  been  carried  to  the  placenta  by  the  umbilical  arteries.  These  also  are 
paired  veins  within  the  embryo,  although  they  form  a  single  trunk  in  the 
umbilical  cord.  They  extend  cranially  on  each  side  through  the  ventro- 
lateral  part  of  the  body  wall  and  join  the  duct  of  Cuvier  (see  below)  in  the 
septum  transversum  (Figs.  201,  202  and  231).  Very  soon  after  the  appear- 
ance of  the  umbilical  veins  two  other  longitudinal  vessels  develop,  one  on 


THE   DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


251 


each  side  of  the  aorta.  In  the  cervical  region  they  lie  dorsal  to  the  branchial 
arches  and  are  called  the  anterior  cardinal  veins  (Figs.  200  and  231).  The 
more  caudal  parts  of  the  vessels  are  situated  in  the  region  of  the  developing 
mesonephros  and  are  called  the  posterior  cardinal  veins  (Figs.  200  and  231). 
At  a  point  about  opposite  the  heart  the  anterior  and  posterior  cardinals  on 
each  side  unite  to  form  a  single  vessel,  the  duct  of  Cuvier,  which  turns  medially 
through  the  septum  transversum  and  opens  into  the  sinus  venosus  (Figs. 
200  and  216).  Thus  three  primary  sets  of  veins  are  formed  at  a  very  early 
stage  of  development:  (i)  The  omphalomesenteric  veins;  (2)  the  umbilical 
veins;  (3)  the  cardinal  veins. 

The  veins  of  the  head  and  neck  regions  are  derivatives  of  the  anterior 
cardinals.  The  proximal  Darts  of  these  vessels  are  present  in  embryos  of 
3.2  mm.;  later  they  extend  cranially  along  the  ventro-lateral  surface  of  the 

N.V  N.VII  N.IX 


Mid.  cerebral  vein 


Sup.  cerebral  vein 


Inf.  cerebral  vein 


•Lat.  vein  of  head 


FIG.  229. — Veins  of  the  head  of  a  9  mm.  human  embryo.     Mall. 

brain  on  the  medial  side  of  the  roots  of  the  cranial  nerves.  The  position 
relative  to  the  nerves  is  only  temporary,  however,  for  collaterals  arising  from 
the  veins  pass  to  the  lateral  side  of  the  nerves  and  enlarge  to  form  the  main 
channels.  The  original  channels  atrophy  except  in  the  region  of  the  trigemi- 
nal  nerves  where  they  still  remain  on  the  medial  side  of  the  nerves  as  the 
forerunners  of  the  cavernous  sinuses.  The  vessel  thus  formed  laterally  to  the 
cranial  nerves  (except  the  trigeminal)  on  each  side  of  the  brain  is  known  as 
the  lateral  vein  of  the  head  (vena  later alis  capitis)  (Fig.  229.)  The  blood  is 
collected  from  the  brain  region  by  small  vessels  which  unite  to  form  three 
main  stems;  one  of  these,  the  superior  cerebral  vein,  opens  into  the  cranial  end 
of  the  cavernous  sinus;  another,  the  middle  cerebral  vein,  opens  into  the  op- 
posite end  of  the  cavernous  sinus;  and  the  third,  the  inferior  cerebral  vein, 
opens  into  the  lateral  vein  of  the  head  behind  the  ear  vesicle  (Figs.  229  and 


252 


TEXT-BOOK  OF   EMBRYOLOGY 


224).  The  branches  of  the  superior  cerebral  vein  extend  over  the  cerebral 
hemispheres  and  unite  with  their  fellows  of  the  opposite  side  to  form  the 
superior  sagittal  sinus  which  lies  in  the  medial  line  (Figs.  224  and  230). 
The  superior  sagittal  sinus  is  at  first  naturally  drained  by  the  superior  cere- 
bral veins;  but  later,  as  the  cerebral  hemispheres  enlarge  and  extend  farther 
toward  the  mid-brain  region,  it  is  carried  back  and  joins  the  middle  cerebral 
vein;  still  later,  for  the  same  reason,  it  joins  the  inferior  cerebral  vein  (Fig. 
230,  A  and  B).  During  these  later  changes  the  connection  between  the 


C Ard.  yety       Sufi.  SAf. 
"Otic  vesicle 


MU.cerel).  vely      Cotft.  of  stf 


vet? 


Coijft.of  si.rj uses 


^  _. 
La,t.veip  o 


FIG.  230. — Diagrams  representing  four  stages  in  the  development  of  the  veins  of  the 
head  in  human  embryos.     M all. 

superior  sagittal  sinus  and  the  superior  cerebral  vein  is  lost  (Fig.  230).  The 
middle  cerebral  vein  becomes  the  superior  petrosal  sinus  which  forms  a  com- 
munication between  the  cavernous  sinus  and  transverse  sinus.  The  trans- 
verse sinus  represents  the  channel  between  the  superior  sagittal  sinus  and  the 
cranial  end  of  the  cardinal  vein;  or  in  other  words,  its  cranial  portion  repre- 
sents the  connection  between  the  superior  sagittal  sinus  and  the  inferior 
cerebral  vein  while  its  caudal  portion  represents  the  inferior  cerebral  vein 
itself  (Fig.  230,  compare  C  and  D).  The  caudal  end  of  the  superior  sagittal 
sinus  becomes  dilated  to  form  the  confluence  of  the  sinuses  (confluens 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


253 


si  tin  urn).  From  the  latter  a  new  vessel  grows  out  to  form  the  straight  sinus, 
and  a  further  growth  from  the  straight  sinus  forms  the  large  vein  of  the 
cerebrum  (vein  of  Galen).  The  inferior  sagittal  sinus  also  represents  a  new 
outgrowth  at  the  point  of  junction  of  the  large  vein  of  the  cerebrum  and 
inferior  sagittal  sinus  (Fig.  230,  D).  During  the  course  of  development  the 
lateral  vein  of  the  head  gradually  atrophies  and  finally  disappears,  and  the 
inferior  petrosal  sinus  probably  represents  a  new  formation  which  extends 
from  the  cavernous  sinus  to  the  transverse  sinus  (Fig.  230,  C  and  D).  At 


Ant.  cardinal 
(int.  jugular) 


Omphalomesenteric 
(vitelline) 


Mesonephro; 


Subcardinal 


Iliac 


FIG.  231. — Diagram  of  the  venous  system  of  a  human  embryo  of  2.6  mm. 
Slightly  modified  from  Kollmann's  Atlas. 

the  point  where  the  inferior  petrosal  joins  the  transverse  sinus  the  latter 
passes  out  of  the  skull  through  the  jugular  foramen  to  become  the  internal 
jugular  vein  (anterior  cardinal).  (Mall.) 

As  stated  in  a  preceding  paragraph,  the  anterior  cardinal  veins  extend 
from  the  ducts  of  Cuvier  to  the  head  region,  passing  to  the  dorsal  side  of  the 
branchial  arches.  They  are  at  first  paired  and  symmetrical,  but,  since  the 
heart  is  situated  in  the  cervical  region,  are  comparatively  short  and  receive 
blood  from  the  cervical  region  through  segmental  branches  which  belong  only 


254 


TEXT-BOOK  OF  EMBRYOLOGY 


to  the  most  cranial  of  the  cervical  segments.  The  other  segmental  cervical 
veins,  including  the  subclavian  veins,  open  at  first  into  the  posterior  cardinals 
(Fig.  231).  Later,  however,  as  the  heart  recedes  into  the  thorax  the  anterior 
cardinal  veins  are  elongated  and  the  segmental  cervical  veins,  including  the 
subclavians,  come  to  open  into  them  (Fig.  233).  The  bilateral  symmetry  is 
then  broken  by  an  anastomosing  vessel  which  extends  obliquely  across  from  a 
point  on  the  left  cardinal  about  opposite  the  subclavian  to  a  point  nearer  the 
heart  on  the  right  subclavian  (Figs.  232,  B,  and  233).  The  portion  of  the  left 
cardinal  cranial  to  the  subclavian  becomes  the  left  internal  jugular  vein  which 


Ant.  cardinal ...... • 


Duct  of  Cuvier  • 
Subclavian « 


Inf.  vena  cava—— 


Post,  cardinal— •• 
Subcardinal.... 


Hiac. 


Ant.  cardinal 
(int.  jugular) 

••—Ext.  jugular 

••Subclavian 
•  Duct  of  Cuvier 
•••  Inf.  vena  cava 
.....  Post,  cardinal 


Post,  cardinal 
Subcardinal 


...    Iliac 


FIG, 


A  B 

232. — Diagrams  of  two  stages  in  the  development  of  the  anterior  and  posterior  cardinal  veins, 
the  Subcardinal  veins  (revehent  veins  of  the  primitive  kidney),  and  the  inferior  vena  cava. 
The  small  branches  of  the  cardinals  and  subcardinals  ramify  in  the  primitive  kidneys 
(mesonephroi).  Slightly  modified  from  Ilochstetter. 


communciates  with  the  intracranial  sinuses.  The  anastomosis  itself  be- 
comes the  left  innominate  vein.  The  portion  of  the  left  cardinal  between  the 
subclavian  and  the  duct  of  Cuvier,  the  duct  of  Cuvier  itself,  and  the  left  horn 
of  the  sinus  venosus  together  form  the  coronary  sinus  (Fig.  234).  On  the 
right  side  the  more  distal  part  of  the  cardinal  becomes  the  internal  jugular 
vein;  the  portion  between  the  subclavian  and  the  anastomosis  (left  innomi- 
nate vein)  becomes  the  right  innominate  vein;  and  the  common  stem  formed 
by  the  latter  and  the  left  innominate  constitutes  the  superior  vena  cava 
which  opens  into  the  right  atrium  (see  p.  236).  The  external  jugular  vein 
on  each  side  appears  later  than  the  superior  cardinal  as  an  independent 


THE   DEVELOPMENT  OF  THE   VASCULAR  SYSTEM 


255 


vessel  which  comes  to  lie  parallel  to  the  internal  jugular  and  opens  into  it 
near  the  subclavian.  The  opening,  however,  shifts  to  the  subclavian, 
where  it  is  usually  found  in  the  adult  (Figs.  323  and  234). 

The  changes  which  occur  in  the  posterior  cardinal  veins  are  very  extensive 
and  result  in  conditions  which  bear  but  little  resemblance  to  those  in  the 
earlier  stages.  In  connection  with  these  changes  the  development  of  the 
inferior  vena  cava  must  be  considered.  The  posterior  cardinal  veins  appear 
very  early  as  paired,  bilaterally  symmetrical  vessels  which  extend  from  the 
duct  of  Cuvier  to  the  tail  region  and  are  situated  ventro-lateral  to  the  aorta 


Ant.  cardinal 
(int.  jugular) 


Ext.  jugular  - 


Innominate  (right) 


Sup.  vena  cava •§- 

Post,  cardinal 
(azygos)     - 

Inf.  vena  cava  — ... 


Subcardinal 


Subcardinal— 


Hiac— 


FlG.  233. — Diagram  representing  a  stage  (later  than  Fig.  232)  in  the  development  of  the  superior 
vena  cava  and  the  inferior  vena  cava,  also  of  the  azygos  vein.     Hochstetter. 

(Fig.  231).  From  the  first  they  receive  blood  from  the  body  wall  through 
segmental  branches,  and  as  the  primitive  kidneys  (mesonephroi)  develop 
they  receive  blood  from  them  also,  as  well  as  from  the  mesentery.  They 
return  practically  all  the  blood  from  the  region  of  the  body  situated  caudal 
to  the  heart,  just  as  the  anterior  cardinals  return  the  blood  from  the  region 
of  the  body  situated  cranial  to  the  heart.  In  other  words,  the  two  sets  of 
cardinal  veins  are  the  body  veins  par  excellence  during  the  earlier  stages  of 
development.  While  the  anterior  set  persists  for  the  most  part  as  permanent 
vessels  and  increases  with  the  development  of  the  body,  the  posterior  set 


256  TEXT-BOOK  OF  EMBRYOLOGY 

undergoes  regressive  changes,  its  function  being  taken  by  a  new  vessel — 
the  inferior  vena  cava. 

Not  long  after  the  appearance  of  the  posterior  cardinals,  another  pair  of 
longitudinal  veins  appears  in  the  medial  part  of  the  mesonephroi.  They 
increase  in  size  as  the  mesonephroi  increase  and  receive  blood  from  the 
latter.  They  also  communicate  with  the  cardinals  by  means  of  transverse 
channels  which,  however,  are  later  broken  up  as  the  mesonephroi  become 
more  complicated  in  structure.  These  vessels  are  known  as  the  subcardinal 
veins,  or  revehent  veins  of  the  primitive  kidneys  (Fig.  232,  A).  After 
they  have  attained  a  considerable  size,  a  large  anastomosis  is  formed  between 
them  ventral  to  the  aorta  and  just  caudal  to  the  omphalomesenteric  (superior 
mesenteric)  artery  (Fig.  232,  B).  In  the  meantime,  a  branch  of  the  ductus 

Int.  jugular 
(ant.  cardinal; — ••••••J  ^    3    '"'Ext.  jugular 

.^^^  v.. — Subclavian 

Innominate  (right) —          ^^^ 

_  —•/———-Innominate  (left) 

Sup.  vena  cava***" 

^^  ^~1 

-Coronary  sinus 


Azygos     ^  e.. 

......  •*»hemiazygos 


(post,  cardinal)  m  ,  Accessory 


"Ty — Hemiazygos 


FIG.  234. — Diagram  of  final  stage  in  the  development  of  the  superior  vena  cava 
and  the  azygos  vein.  (Compare  with  Fig.  233.) 

venosus  (see  p.  260)  grows  caudally  through  the  dorsal  part  of  the  liver  and 
the  mesentery,  and  joins  the  right  subcardinal  vein  a  short  distance  cranial 
to  the  above  mentioned  anastomosis  (Fig.  232,  A  and  B).  This  branch 
forms  the  proximal  part  of  the  inferior  vena  cava.  At  the  same  time,  also, 
each  subcardinal  forms  a  direct  connection  with  the  corresponding  cardinal 
at  a  point  opposite  the  first  anastomosis;  consequently  the  inferior  vena 
cava,  the  subcardinals  and  the  cardinals  are  all  in  direct  communication 
(Fig.  232,  B).  Thus  two  ways  are  formed  by  which  the  blood  may  return 
to  the  heart:  It  may  return  via  the  cardinals  and  ducts  of  Cuvier,  and  via 
the  inferior  vena  cava. 

It  is  obvious  that  while  these  conditions  exist,  that  is,  while  the  mesonephros  is  func- 
tional, and  blood  is  carried  to  it  by  the  cardinal  veins  and  from  it  by  the  subcardinal  veins, 
there  is  a  true  renal  portal  system.  The  blood  from  the  body  walls  and  lower  extremities 


THE   DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


257 


is  collected  by  the  segmental  vessels  and  poured  into  the  cardinal  veins  and  is  then  dis- 
tributed in  the  mesonephros  by  smaller  channels  or  sinusoids  (Minot),  whence  it  is 
collected  and  carried  off  by  the  subcardinal  veins.  This  passage  of  blood  through  purely 
venous  channels  simulates  the  conditions  in  the  liver  where  there  is  a  true  hepatic  portal 
system. 

From  this  time  on,  the  changes  are  largely  regressions  in  the  cardinal  and 
subcardinal  systems,  corresponding  to  the  atrophy  of  the  mesonephroi,  and 
rapid  increase  in  the  vena  cava  and  its  branches.  The  cranial  end  of  each 
cardinal  becomes  smaller;  the  left  loses  its  connection  with  both  the  vena  cava 
and  the  duct  of  Cuvier,  the  right  its  connection  with  the  vena  cava  only  (Fig. 


Aorta 


Post,  cardinal  vein 
Mesonephric  duct' 

Omphalomesenteric    artery 
Right  umbilical  vei 

Intestine 


Post,  cardinal  vein 


Dorsal  mesentery 
Ccelom 


Left  umbilical  vein 


FIG.  235. — From  a  transverse  section  of  a  5  mm.  human  embryo,  at  the  level  of  the 
omphalomesenteric  (vitelline,  superior  mesenteric)  artery. 

234;.  Subsequent  changes  in  these  parts  of  the  cardinals  will  be  considered 
in  the  following  paragraph.  For  a  time  the  caudal  ends  of  the  two  cardinals 
are  of  equal  importance.  Later,  however,  the  right  becomes  larger,  while  the 
left  atrophies.  The  right  thus  becomes  a  direct  continuation  and  really  a 
part  of  the  vena  cava  (Figs.  233  and  236).  This  is  brought  about,  of  course, 
by  the  original  anastomosis  between  the  vena  cava  and  the  subcardinal  and 
cardinal.  On  the  left  side  the  anastomosis  persists  simply  as  the  proximal 
part  of  the  renal  vein  (Fig.  236) ;  on  the  right  side  the  renal  vein  is  a  new 
structure  which  develops  after  the  kidney  has  attained  practically  its  final 
position,  and  opens  into  the  vena  cava  secondarily.  The  inferior  vena  cava 


258 


TEXT-BOOK  OF  EMBRYOLOGY 


itself  is  a  composite  vessel  derived  from  four  different  anlagen.  i.  The 
part  which  extends  from  the  ductus  venosus  to  the  right  subcardinal  is  of 
independent  origin.  2.  A  short  portion  is  derived  from  a  part  of  the  right 
subcardinal.  3.  Another  short  portion  is  derived  from  the  cross-anastomosis 
between  the  subcardinals  and  cardinals.  4.  The  caudal  end  is  a  derivative 
of  the  caudal  part  of  the  right  cardinal  (compare  Figs.  232,  233,  236.) 

Before  the  caudal  end  of  the  left  cardinal  vein  atrophies,  an  interesting 
and  important  change  occurs  in  the  relations  of  the  ureters  and  cardinals. 
Primarily  the  cardinal  veins  develop  to  the  ventral  side  of  the  ureters.  But 
later  a  collateral  of  each  cardinal  develops  to  the  dorsal  side  of  the  ureter. 
These  join  the  cardinal  cranial  and  caudal  to  the  ureter.  In  other  words,  a 


Inf.  vena  cava    "" 

Suprarenal  gland j'- 

Suprarenal  vein  (right) 


Renal  vein  (right)    — f  " 


Int.  spermatic  (right)  — 
Ureter 


Inf.  vena  cava 
(right  post,  cardinal) 


Common  iliac  (right) , 


£_  vena  cava 


,-;X  _______  Suprarenal  gland 

._  ----  Suprarenal  vein  (lefti 
».*...  Kidney 

\-  ......  Renal  vein  (left) 

Int.  spermatic"(left) 
(post,  cardinal) 

^  .....  Ureter 


Common  iliac  (left) 

.....  Ext.  iliac 
'* Int.  iliac 

r?T^  Common  iliac  (right) 
^A  B^ 

FIG.  236. — Diagrams  representing  final  stages  in  the  development  of  the  inferior  vena  cava 
(compare  with  Fig.  233).     Slightly  modified  from  Hochstetter. 

venous  loop  is  formed  around  the  ureter  (Fig.  233).  The  ventral  arm  of  the 
loop  then  atrophies  and  disappears,  leaving  the  dorsal  arm  as  the  direct  part 
of  the  cardinal  vein.  On  the  right  side,  where  the  cardinal  persists  as  a 
portion  of  the  vena  cava,  the  latter  vessel  comes  to  lie  ventral  to  the  ureter 
(Fig.  236,  A).  On  the  left  side  the  cardinal  atrophies,  leaving  only  the  por- 
tion cranial  to  the  loop  as  the  proximal  end  of  the  internal  spermatic  (testicular 
or  ovarian )  vein  (Fig.  236,  B).  Since  on  the  left  side  the  original  anastomosis 
between  the  subcardinals  and  cardinals  persists  as  the  renal  vein,  the  left 
internal  spermatic  is  a  branch  of  the  renal.  The  right  internal  spermatic 
vein  probably  represents  a  branch  of  the  vena  cava  which  is  independent 
of  the  cardinal. 

In  the  cat  embryo  the  venous  loop  around  the  ureter  is  much  more 


THE   DEVELOPMENT  OF  THE   VASCULAR   SYSTEM 


259 


extensive  than  in  the  other  forms.  The  dorsal  arm  of  the  loop,  named  the 
supracardinal  vein,  extends  from  the  iliac  vein  to  the  original  anastomosis 
between  the  subcardinals  and  cardinals.  In  the  course  of  further  develop- 
ment the  supracardinals  approach  each  other  and  finally  fuse,  forming  a 
large  single  vessel  which  becomes  the  portion  of  vena  cava  caudal  to  the 
renal  veins.  In  this  event  the  portions  of  both  cardinals  forming  the  ventral 
arms  of  the  venous  loops  atrophy  and  disappear. 

Xear  the  caudal  end  of  each  cardinal  vein  a  branch  arises  which  receives 
the  blood  from  the  corresponding  lower  extremity.  Then  a  transverse 
anastomosis  appears  between  the  two  cardinals  at  this  point  (Fig.  236,  A). 
Since  the  portion  of  the  left  cardinal  caudal  to  the  renal  vein  atrophies,  the 
anastomosis  itself  constitutes  the  left  common  iliac  vein  (Fig.  236,  B).  The 
right  common  iliac  is,  of  course,  the  original  branch  of  the  right  cardinal. 
As  the  iliacs  enlarge  they  form  the  two  great  branches  of  the  vena  cava. 


— i)uct  cf  Cuvier.' 


Duct  of  Cuviet- 


Right  umbilical  - 


Right  omphalomesenteric  •- 


— — Ductus  venosus 


..Left  umbilical 


Left  omphalomesenteric 


FIG.  237. — Diagrams  illustrating  two  stages  in  the  transformation  of  the  omphalomesenteric 
and  umbilical  veins  in  the  liver.     Hochstetter. 

With  the  atrophy  of  the  mesonephroi,  the  subcardinal  veins  diminish  in 
size  and  finally  disappear  for  the  greater  part.  The  part  of  the  right  sub- 
cardinal  cranial  to  the  point  of  junction  with  the  vena  cava  disappears- 
entirely.  The  portion  of  the  left  subcardinal  cranial  to  the  anastomosis 
between  the  two  subcardinals  becomes  much  reduced  in  size,  but  persists 
as  the  left  suprarenal  vein.  The  left  suprarenal  vein  is  thus  a  branch  of  the 
left  renal  vein,  since  the  latter  represents  the  anastomosis  itself  (Figs.  232, 
233?  236).  The  right  suprarenal  vein  probably  does  not  represent  a  per- 
sistent right  subcardinal,  but  is  a  new  vessel  opening  into  the  vena  cava. 
The  portion  of  each  subcardinal  caudal  to  the  anastomosis  probably  dis- 
appears entirely,  but  this  has  not  been  definitely  determined. 

The  observations  on  the  development  of  the  azygos  veins  in  the  human 
embryo  are  only  fragmentary.  In  the  rabbit  the  portions  of  the  posterior 
cardinal  veins  immediately  cranial  to  the  anastomosis  between  the  sub- 


260  TEXT-BOOK  OF  EMBRYOLOGY 

cardinals  and  cardinals,  that  is,  just  cranial  to  the  renal  veins,  disappear. 
The  more  cranial  portion  of  the  right  cardinal  persists  as  the  azygos  vein 
which  receives  the  intercostal  (segmental)  branches  and  opens  into  the 
superior  vena  cava.  An  oblique  anastomosis  is  formed,  dorsal  to  the  aorta, 
between  the  two  cardinals  (Fig.  233).  This  anastomosis  and  the  portion  of 
the  left  cardinal  caudal  to  it  together  form  the  hemiazygos  vein.  The  por- 
tion of  the  left  cardinal  cranial  to  the  anastomosis  loses  its  connection 
with  the  duct  of  Cuvier  (or  coronary  sinus)  and  becomes  the  accessory 
hemiazygos  vein  (Fig.  234).  The  ascending  lumbar  veins,  which  join  the 
azygos  and  hemiazygos,  probably  do  not  represent  persistent  parts  of  the 
caudal  ends  of  the  cardinals,  but  are  formed  by  longitudinal  anastomoses 
between  the  original  segmental  lumbar  veins. 

The  changes  which  occur  in  the  region  of  the  liver  are  of  much  im- 
portance and  result  in  conditions  which  bear  no  resemblance  to  the  primary 
ones.  As  has  already  been  noted,  the  omphalomesenteric  veins  enter  the 
body  at  the  umbilicus,  pass  cranially  along  the  intestine  and  open  into  the 
caudal  end  of  the  heart.  The  umbilical  veins,  which  appear  soon  after, 
enter  the  body  at  the  umbilicus  and  pass  cranially,  one  on  each  side,  in  the 
ventro-lateral  part  of  the  body  wall;  at  the  level  of  the  heart  they  turn 
mesially  through  the  septum  transversum  and  join  the  corresponding 
omphalomesenteric  veins  to  form  a  common  trunk  on  each  side,  into  which 
the  duct  of  Cuvier  then  opens  (Fig.  231).  When  the  liver  grows  out  as  an 
evagination  from  the  intestine,  it  comes  in  contact  with  the  proximal  ends 
of  the  omphalomesenteric  veins  and,  as  it  enlarges,  breaks  them  up  into 
numerous  smaller  channels  (Fig.  237). 

The  blood  then,  instead  of  having  a  direct  channel,  is  forced  to  flow 
through  these  smaller  channels  which  have  been  termed  sinusoids.  When 
the  liver  has  attained  a  considerable  size  a  more  direct  and  definite  channel 
is  formed,  which  extends  through  the  substance  of  the  liver  from  the  proximal 
end  of  the  right  omphalomesenteric  vein  obliquely  caudally  to  the  left 
omphalomesenteric  vein.  This  newly  formed  channel  is  the  ductus  venosus 
(Figs.  237  and  238).  In  the  meantime,  three  transverse  anastomoses  develop 
between  the  omphalomesenteric  veins  just  caudal  to  the  liver.  The  middle 
one  is  dorsal  to  the  intestine,  the  other  two  ventral,  so  that  the  intestine  is 
surrounded  by  two  venous  loops  or  rings  (Figs.  237  and  238).  At  the  same 
time  a  cross-anastomosis  develops  between  the  left  umbilical  vein,  which  is 
primarily  the  smaller,  and  the  corresponding  omphalomesenteric.  This 
anastomosis  joins  the  omphalomesenteric  at  about  the  point  where  the  latter 
joins  the  ductus  venosus,  so  that  it  seems  to  be  a  continuation  of  the  ductus 
venosus.  A  similar  cross-anastomosis  also  develops  between  the  right  um- 
bilical and  right  omphalomesenteric  (Figs.  327  and  238).  Thus  the  blood 


THE   DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


261 


that  is  brought  in  from  the  placenta  by  the  umbilical  veins  may  pass  through 
the  liver.  Then  the  portion  of  each  umbilical  between  the  anastomosis  and 
the  duct  of  Cuvier  atrophies  and  disappears  (Fig.  238).  The  remaining 
portion  of  the  left  umbilical,  which  was  originally  the  smaller,  gradually 
increases  in  size  and  finally  carries  all  the  blood  from  the  placenta.  The 
right  umbilical,  on  the  other  hand,  loses  its  connection  with  the  liver  and 
persists  only  as  a  small  vein  in  the  body  wall,  which  opens  into  the  left 
umbilical  vein  near  the  umbilical  cord  (Fig.  239).  Thus  there  is  the  peculiar 
phenomenon  of  a  vessel  carrying  blood  in  different  directions  at  different 
periods  of  its  history.  During  the  course  of  development  of  the  septum 


CEsophagus 


Ant.  cardinal 


Post,  cardinal 

Liver 
Right  umbilical 

Venous  ring 
Venous  ring 


Duct  of  Cuvier 
Left  umbilical 
Ductus  venosus 


Left  umbilical 


Om  phalomesenteric 
Intestine 


FIG.  238. — Veins  in  the  liver  region  of  a  human  embryo  of  4  mm.     His,  Kollmann's  Atlas. 

transversum  and  diaphragm  the  left  umbilical  is  withdrawn  from  the  body 
wall  and  passes  directly  from  the  umbilicus  to  the  ventral  side  of  the  liver. 
During  foetal  life  it  conveys  all  the  blood  from  the  placenta  to  the  liver.  A 
part  of  the  blood  is  distributed  in  the  liver,  a  part  is  carried  directly  to  the 
inferior  vena  cava  by  the  ductus  venosus  (Fig.  240).  After  birth  the 
placental  blood  is  cut  off  and  the  umbilical  vein  degenerates  to  form 
the  round  ligament  of  the  liver. 

The  venous  rings  around  the  intestine  also  undergo  marked  changes. 
The  right  side  of  the  most  caudal  and  the  left  side  of  the  most  cranial  dis- 
appear; the  remaining  vessel  finally  loses  its  connection  with  the  ductus 
venosus  and  becomes  the  portal  vein  (Figs.  237,  238,  239  and  240).  The 


262 


TEXT-BOOK  OF  EMBRYOLOGY 


portal  vein  is  thus  a  derivative  of  the  omphalomesenterics.  After  birth, 
when  the  placental  blood  is  cut  off,  blood  is  distributed  in  the  liver  by 
branches  of  the  portal  vein,  which  represent  the  advehent  hepatic  veins; 
it  is  collected  again  by  branches  which  unite  to  form  the  revehent  hepatic 
veins,  or  hepatic  veins  proper,  and  the  latter  open  into  the  inferior  vena 
cava.  The  advehent  and  revehent  hepatic  veins  are  formed  by  the 
enlargement  of  some  of  the  original  sinusoids  (Figs.  237  and  239). 

Observations  on  the  development  of  the  veins  in  the  extremities  of  human 


Ant.  cardinal 
(int.  jugular) 


Post,  cardinal 


Sinus  venosus  and 
orifice  of  ductus  venosus 


Revehent  hepatic 


Advehent  hepatic 


Right  umbilical 


Omphalomesenteric 
(portal) 


Umbilical  vein 


Ant.  cardinal 
(int.  jugular) 


Post,  cardinal 
Bronchus 

Revehent  hepatic 
Advehent  hepatic 

Left  umbilical 
Umbilical  cord 


FIG.  239. — Veins  in  the  liver  region  of  a  human  embryo  of  10  mm.     Kollmann's  Alias. 

embryos  are  so  fragmentary  that  it  seems  advisable  to  make  use  of  the  work 
that  has  been  done  on  the  rabbit.  In  the  upper  extremity  the  first  vein  to 
develop  is  the  primary  ulnar  vein  which  begins  in  the  radial  (cranial)  side  of 
the  extremity  near  its  proximal  end,  extends  distally  along  the  radial  border, 
thence  proximally  along  the  ulnar  (caudal)  border,  and  opens  into  the 
anterior  cardinal  vein  (internal  jugular)  near  the  duct  of  Cuvier  (Fig.  241). 
This  condition  is  present  in  rabbit  embryos  of  thirteen  days.  A  little  later  a 
second  vessel,  the  cephalic  vein,  appears  as  a  branch  of  the  external  jugular, 


THE   DEVELOPMENT  OF  THE   VASCULAR   SYSTEM 


263 


extends  along  the  radial  side  of  the  extremity  and  becomes  connected  with 
the  digital  veins  (Fig.  242).  When  the  digital  veins  are  taken  up  by  the 
cephalic,  the  distal  portion^  of  the  primitive  ulnar  undergoes  regression. 
These  changes  have  taken  place  in  rabbit  embryos  of  fifteen  days,  and  for  a 
short  period  the  cephalic  vein  is  the  chief  vessel  of  the  extremity.  The 
primitive  ulnar  vein,  however,  develops  more  rapidly  than  the  cephalic  and, 


Heart- 


Inf.  vena  cava— •- 


Ductus  venosus 


Left  lobe  of  liver- 


Umbilical  vein 


Umbilical  ring  — 


Hepatic  veins 


Right  lobe  of  liver 


Gall  bladder 


Portal  vein 
(omphalomesenteric; 


Intestine 


—Inf.  vena  cava 


FIG.  240. — Veins  of  the  liver  (seen  from  below)  of  a  human  foetus  at  term      Kollmann's  Atlas. 


with  its  branches,  soon  becomes  the  chief  vessel;  the  portion  in  the  forearm 
gives  rise  to  either  the  ulnar  or  basilic  vein;  the  portion  in  the  arm  becomes 
the  brachial  vein  which  then  passes  over  into  the  axillary,  and  the  latter 
in  turn  passes  over  into  the  subclavian.  The  cephalic  vein  of  the  embryo 
persists  as  the  cephalic  of  the  adult,  and,  during  the  period  when  it  forms  the 
chief  vessel  of  the  extremity,  a  branch  arises  from  it  which  becomes  the  radial 
vein.  Primarily  the  cephalic  vein  opens  into  the  external  jugular,  but  later 


264 


TEXT-BOOK  OF  EMBRYOLOGY 


Atjt.  ca.r<L. 


a  new  connection  is  formed  with  the  axillary,  while  the  original  connection 

persists  as  the  j ugulocephalic  (Fig.  243). 

In  a  rabbit  embryo  of  ten  and  one-half  days  a  vein  follows  the  border  of 
the  lower  extremity  all  the  way  round,  connecting 
on  the  cranial  side  with  the  umbilical  and  on  the 
caudal  side  with  the  posterior  cardinal.  This  is  the 
primitive  fibular  vein,  and  from  its  course  is  homol- 
ogous with  the  primitive  ulnar  vein  of  the  upper 
extremity  (Fig.  241).  From  this  time  on,  how- 
ever, the  course  of  development  in  the  lower  ex- 
tremity differs  from  that  in  the  upper.  The  con- 
nection of  the  fibular  vein  with  the  umbilical  is 
soon  lost.  In  older  embryos  (fifteen  days)  two 
branches  of  the  fibular  vein  have  appeared;  one 
of  these,  the  anterior  tibial  vein,  _  begins  on  the 
embryo  of  14  days  (u  mm.),  dorsum  of  the  foot  and  extends  diagonally  proxi- 

Modified  from  Lewis.  .  .        .,  ,    , 

mally,   to   open   into  the  fibular  in  the  caudal 

border;  the  other,  the  so-called  connecting  branch,  begins  as  twigs  in  the  ab- 
dominal wall  and  tibial  side  of  the  extremity  and  opens  into  the  fibular  just 
proximal  to  the  opening  of  the  anterior  tibial  (Fig.  242).  Later  the  distal 


FIG.  242.  FIG.  243. 

FIG.  242. — Diagram  of  the  veins  in  the  extremities  of  a  rabbit  embryo  of  14  days 

and  18  hours  (14.5  mm.).     Modified  from  Lewis. 

FIG.  243. — Diagram  of  the  veins  in  the  extremities  of  a  rabbit  embryo  of  17  days 
(21  mm.).     Modified  from  Lewis. 

part  of  the  primitive  fibular  is  broken  up  by  the  differentiation  of  the  digits 
(toes)  and  disappears  almost  up  to  the  point  of  junction  with  the  anterior 
tibial.  The  latter  enlarges  and  receives  the  digital  branches,  and  appears 


THE  DEVELOPMENT  OF  THE   VASCULAR   SYSTEM 


265 


as  a  continuation  of  the  proximal  part  of  the  primitive  fibular.  The  anterior 
tibial  and  primitive  fibular  together  thus  constitute  the  sciatic  vein  (Fig. 
243).  Another  vessel  appears  in  embryos  of  fifteen  days,  which  represents 
the  beginning  of  the  femoral  vein  and  opens  into  the  cardinal,  cranial  to  the 
opening  of  the  sciatic  (Fig.  243).  From  this  time  on  the  femoral,  with  its 
branches,  enlarges  at  the  expense  of  the  other  veins  and  becomes  the  principal 
vein  of  the  lower  extremity.  In  the  human  embryo  the  femoral  anastomoses 
with  the  sciatic  near  the  knee  and  the  proximal  portion  of  the  sciatic  then 
atrophies,  the  distal  portion  persisting  as  the  small  scphenous  vein.  The 


Sup.  vena  cava 
Lungs 

Right  atrium 

Right  ventricle 

Inf.  vena  cava 

Liver 

Ductus  venosus 

Placenta 

Inf.  vena  cava 

Umbilical  vein 
Umbilical  artery 


Ant.  part  cf  body 


Carotid  and 
subclavian  arteries 

Ductus  arteriosus 


Pulmonary  artery 
Left  ventricle 


Post,  part  of  body 


FIG.  244. — Diagram  illustrating  the  foetal  circulation.     Compare  with  Fig.  245. 

Modified  from  Kollmann. 

The  shading  represents  the  relative  impurity  of  the  blood  in  different  regions,  the 
darkest  shading  representing  the  most  impure  blood 

large  saphenous  vein  and  the  posterior  tibial  vein  possibly  are  derivatives  of 
the  femoral,  but  this  question  has  not  been  settled. 

CHANGES  IN  THE  CIRCULATION  AT  BIRTH. — During  fcetal  life  the  course  of 
the  blood  is  adapted  to  the  placental  circulation,  since  the  placenta  is  the 
only  means  by  which  the  blood  is  purified  and  from  which  the  foetus  derives 
its  nutriment.  The  pure  blood  from  the  placenta  passes  through  the  umbil- 
ical vein  to  the  liver;  there  a  part  of  it  is  distributed  to  the  liver  by  some  of 
the  advehent  veins,  is  collected  again  by  the  revehent  veins  and  poured  into 
the  inferior  vena  cava;  a  part  passes  directly  to  the  vena  cava  through  the 


266 


TEXT-BOOK   OF   EMBRYOLOGY 


ductus  venosus.  At  this  point  the  blood  acquires  some  impurity  from  the 
stream  brought  in  by  the  vena  cava  itself  and  the  portal  vein.  The  slightly 
impure  blood  then  flows  into  the  right  atrium,  is  directed  by  the  Eustachian 
valve  through  the  foramen  ovale  into  the  left  atrium,  thence  flows  into  the 
left  ventricle  and  is  forced  out  into  the  aorta.  A  part  of  the  blood  flows  on 
through  the  aorta,  a  part  is  carried  to  the  upper  extremities  and  head  and 
neck  regions  by  the  subclavian  and  carotid  arteries.  The  latter  part,  then 
becoming  impure,  is  carried  back  to  the  right  atrium  by  the  subclavian 


Sup.  vena  cava 
Lungs 

Pulmonary  veins 
Right  atrium 

Right  ventricle 
Inf.  vena  cava 

Hepatic  vein 
Liver 


Inf.  vena  cav 


Ant.  part  cf  body 


Carotid  and 
subclavian  arteries 


Pulmonary  artery 


Left  ventricle 


Aorta 


Hepatic  artery 


Portal  vein 

Intestinal 
circulation 


Post,  part  of  body 


FIG.  245. — Diagram  illustrating  the  circulation  in  the  adult.     Compare  with  Fig.  244.     The 
shading  represents  the  relative  impurity  of  the  blood,  the  white  being  the  purest  blood. 

and  jugular  veins  and  superior  vena  cava;  from  the  right  atrium  the  greater 
portion  flows  into  the  right  ventricle  and  thence  is  forced  out  into  the  large 
pulmonary  artery.  But  since  the  lungs  are  non-functional,  this  blood  passes 
through  the  ductus  arteriosus  to  join  the  stream  in  the  aorta.  The  blood 
received  by  the  more  cranial  portion  of  the  foetus  is  but  slightly  impure, 
for  the  impure  blood  from  the  ductus  arteriosus  joins  the  aortic  stream  distal 
to  the  origin  of  the  subclavian  and  carotid  arteries.  This  accounts  for 
the  fact  that  the  more  cranial  portion  of  the  body  generally  is  better  devel- 
oped than  the  more  caudal  portion.  It  is  well  to  note  here  that  the  liver 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM  267 

receives  purer  blood  than  any  other  part  of  the  body,  and  this  is  undoubtedly 
correlated  with  the  relatively  enormous  size  of  that  organ  in  the  foetus. 
The  rather  impure  blood  which  starts  through  the  dorsal  aorta  is  in  part 
distributed  to  the  viscera,  body  walls,  and  lower  extremities  by  the  visceral 
and  segmental  arteries,  and  thence  is  collected  by  the  branches  of  the  portal 
vein  and  inferior  vena  cava  to  be  returned  as  impure  blood  to  the  umbilical 
current  at  the  liver;  in  part  it  is  carried  by  the  umbilical  arteries  to  the  pla- 
centa, there  to  be  purified  and  collected  by  the  branches  of  the  umbilical 
vein  (see  Fig.  244). 

At  birth,  when  the  placental  circulation  is  cut  ofT,  the  proximal  end  of  the 
umbilical  vein  atrophies  to  form  the  round  ligament  of  the  liver;  the  ductus 
venosus  also  atrophies  and  becomes  merely  a  connective-tissue  cord  in  the 
liver.  The  hepatic  portal  circulation  is  still  maintained  by  the  portal  vein. 
The  foramen  ovale  is  closed  and  the  impure  blood  from  the  inferior  vena  cava 
as  well  as  that  from  the  superior,  passes  from  the  right  atrium  into  the  right 
ventricle  and  thence  is  forced  out  through  the  pulmonary  artery  to  the  lungs, 
which  at  this  time  become  functional,  and  is  returned  to  the  left  atrium  by  the 
pulmonary  veins.  The  ductus  arteriosus  atrophies  to  form  the  ligamentum 
arteriosum.  From  the  left  atrium  the  pure  blood  flows  into  the  left  ventricle, 
thence  is  forced  out  through  the  aorta  and  its  branches  to  all  parts  of  the 
body.  At  the  same  time  the  more  distal  portions  of  the  umbilical  arteries  in 
the  embryo  atrophy  to  form  the  lateral  umbilical  ligaments,  their  proximal 
portions  persisting  as  the  superior  vesical  arteries  (see  Fig.  245). 

Haemopoiesis — Histogenesis  of  the  Blood  Cells. 

Two  sharply  contrasting  views  are  held  regarding  the  origin  and  genetic 
relationships  of  the  different  kinds  of  blood  cells.  The  one  view,  expressed 
in  the  monophyletic  theory,  holds  that  there  is  differentiated  out  of  the  mesen- 
chyme  a  certain  type  of  cells — the  primitive  blood  cells,  or  haemoblasts — 
and  that  from  this  single  type  all  the  cells  of  the  blood  arise  through  proc- 
esses of  development  along  divergent  lines.  The  other  view,  expressed  in 
the  polyphyletic  theory,  holds  that  while  the  blood  cells  are  of  mesenchymal 
origin  the  red  cells  and  white  cells  have  a  dual  origin,  each  type  arising  from 
its  own  mother-cells ;  and  further  that  perhaps  each  kind  of  white  cells  arises 
from  a  distinct  parent-cell.  The  recent  extensive  studies  of  the  problem 
have  yielded  evidence  that  turns  the  balance  at  present  in  favor  of  the  mono- 
phyletic theory,  and  the  following  account  is  based  in  the  main  upon  these 
studies,  particularly  those  of  Maximow  on  the  rabbit  and  Dantschakoff  on 
the  chick. 

The  sites  of  blood  formation,  or  haemopoiesis,  are  (i)  the  area  opaca 


268 


TEXT-BOOK  OF   EMBRYOLOGY 


(yolk  sac),  (2)  the  body  mesenchyme,  including  the  endotheiium  of  the  early 
blood  vessels,  (3)  the  liver  and  spleen,  (4)  bone  marrow,  and  (5)  the  lymph 
glands.  These  various  structures  are  functional  at  successive  periods  of 
development  of  the  embryo,  but  overlap  to  a  certain  extent,  the  marrow  and 
lymph  glands  being  probably  the  only  foci  of  origin  of  blood  cells  in  the  adult. 
In  the  area  opaca  blood-cell  development  is  initiated  in  the  formation  of 
the  blood  islands.  Some  of  the  mesenchymal  cells  become  less  irregular  in 
shape  by  retraction  of  their  protoplasmic  processes  and  isolation  from  the 
general  syncytium.  They  assume  amoeboid  properties  and  the  cytoplasm 


** 


FIG.  246. — Mesenchyme  from  a  rabbit  embryo  at  the  time  of  beginning  blood  formation. 

Maximow. 

m,  Ordinary  mesenchyme  cells;  mf,  mesenchyme  cell  in  mitosis;  /,  primitive  blood  cell 

(primitive   lymphocyte). 

acquires  a  distinctly  basophilic  character  (Fig.  246).  These  then  represent 
primitive  blood  cells,  or  hcemoblasts.  Maximow  has  given  them  the  name 
primitive  lymphocytes,  or  lymphoblasts,  regarding  them  as  the  common  an- 
cestors of  all  the  blood  cells.  Clusters  of  these  cells  constitute  the  blood 
islands  which  are  involved  in  the  development  of  the  primitive  blood  spaces, 
the  superficial  cells  being  transformed  into  endotheiium  (see  p.  217)  and  the 
central  cells  remaining  as  primitive  lymphocytes.  Other  primitive  lympho- 
cytes also  differentiate  in  the  mesenchyme  outside  of  the  blood  spaces, 
afterward  probably  entering  the  vessels  by  virtue  of  their  amoeboid  properties. 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


269 


There  is  a  view  that  both  the  blood  cells  and  the  endothelium  of  blood 
vessels  arise  from  certain  mesamceboid  cells  of  entodermal  origin,  which  are 
insinuated  between  the  entoderm  and  mesoderm  but  are  not  in  the  strict 
sense  constituents  of  the  latter,  and  which  collectively  have  been  called  the 
angioblast.  While  the  mesamceboid  cells  are  probably  identical  with  the 
primitive  lymphocytes,  the  idea  that  they  constitute  a  set  of  specific  rudi- 
ments of  entodermal  origin,  from  which  both  blood  cells  and  endothelium 
arise,  has  not  been  generally  accepted.  The  view,  however,  is  not  discord- 
ant with  the  monophyletic  concept  of  the  origin  of  blood  cells. 


FIG.  247. — Portion  of  a  blood  vessel  from  the  yolk  sac  of  a  rabbit  embryo,  showing  various 

stages  in  the  formation  of  erythrocytes.     Maximow. 
0,  megaloblasts;  a',  megaloblast  in  mitosis;  b,  normoblasts;  b',  normoblast  in  mitosis;  c,  erythro- 

blasts;    d,   erythrocyte,    not   yet   discoid;   en,    endothelium;   /,    primitive   lymphocytes; 

k,  normoblast  recently  divided;  n,  shrunken  erythroblasts  (?);  n',  extruded  nucleus. 

The  primitive  lymphocytes  (of  Maximow),  constituting  the  parent  stem 
from  which  all  the  blood  cells  arise  according  to  the  monophyletic  theory, 
specialize  at  first  in  two  general  directions.  In  one  direction  the  specializa- 
tion leads  toward  the  erythrocytes,  or  red  blood  corpuscles,  and  in  the  other 
toward  the  leucocyte,  or  white  blood  cell,  series  including  the  myelocytes. 
In  the  former  case  the  lymphocytes  become  modified  in  that  the  cytoplasm 
becomes  less  basophilic  and  acquires  a  trace  of  haemoglobin;  the  nuclei  become 


270 


TEXT-BCOK  OF   EMBRYOLOGY 


somewhat  eccentric,  the  chromatin  network  a  little  denser  and  the  nucleoli 
less  conspicuous.  While  these  changes  are  in  progress  the  cells  multiply  by 
mitosis.  The  resulting  cells  are  termed  megaloblasts  (Fig.  247,  a).  These 
continue  to  multiply  by  mitosis,  the  cytoplasm  acquiring  more  haemoglobin 
and  the  nuclei  becoming  more  dense,  the  resulting  cells  being  somewhat 
smaller  and  known  as  normoblasts  (Fig.  247,  b).  The  normoblasts,  still  divid- 
ing by  mitosis,  acquire  still  more  haemoglobin  and  become  erythroblasts  (Fig. 
247,  c).  These  lose  their  nuclei  and  thus  become  erythrocytes,  the  definitive 
red  blood  corpuscles.  The  manner  in  which  the  nuclei  are  lost  is  a  matter 
of  dispute.  Some  claim  it  is  absorbed  (karyolysis) ;  others  claim  it  is  extruded 

(karyorrhexis)  (Fig.  248) ;  recently  the 
observation  has  been  made  that  the 
nucleus  with  a  small  amount  of  sur- 
rounding cytoplasm  escapes  from  the  cell 
in  a  manner  resembling  constriction. 

In  the  specialization  leading  to  the 
white  blood  cell  series,  the  parent  stem 
cell  (primitive  lymphocyte)  proliferates 
by  mitosis  and  undergoes  certain  di- 
vergent changes  in  its  nucleus  and  cyto- 
plasm which  yield  the  characters  of  the 
various  kinds  of  leucocytes.  Some  of 
the  cells  become  polymorphonuclear  and 
acquire  neutrophile  granules  to  become 
neutrophile  leucocytes;  others  acquire 
acidophile  granules  as  acidophiles;  still 
others,  basophile  granules  as  basophiles. 
The  large  mononuclear  leucocytes,  with  the  transitional  forms  having  the 
horseshoe-shaped  nuclei,  possibly  represent  but  slightly  modified  primitive 
lymphocytes.  The  definitive  lymphocytes  are  probably  derived  from  the 
primitive  by  division  and  but  slight  changes  in  character.  Thus  the  vari- 
ous forms  of  white  blood  cells  would  not  represent  different  stages  in  a  series 
but  divergent  lines  of  specialization  from  a  parent  stem. 

As  mentioned  before,  the  various  blood  forming  organs  function  as  such 
at  successive  stages  of  development  of  the  embryo.  The  mesenchyme 
generally,  both  in  the  yolk  sac  and  in  the  body,  gives  rise  to  blood  cells  during 
the  earlier  stages  and  may  continue  to  do  so  until  relatively  late  in  embryonic 
life  as  has  been  demonstrated  in  the  chick.  It  is  interesting  to  note  in  this 
connection  that  in  certain  regions  endothelial  cells  may  also  be  transformed 
into  primitive  blood  cells.  In  the  earlier  stages  of  liver  development  active 
haemopoiesis  is  observed  in  the  sinusoids,  probably  partly  from  cells  carried  in 


FIG.  248. — Showing  the  escape  of  the  nuclei 
from  nucleated  red  blood  cells.  Howell. 

I,  2,  3,  4,  represent  stages  of  extrusion 
observed  in  living  cells;  a,  from  circulat- 
ing blood  of  adult  cat  after  bleeding  four 
times;  b,  from  young  kitten  after  bleed- 
ing; c,  from  90  mm.  cat  embryo;  others 
from  marrow  of  adult  cat. 


THE   DEVELOPMENT  OF  THE  VASCULAR   SYSTEM 


271 


by  the  blood  stream  and  partly  from  primitive  blood  cells  derived  from  the 
neighboring  mesenchyme  (Fig.  249).  This  function  ceases  in  the  liver  in  later 
embryonic  life.  The  formation  of  blood  cells  takes  place  in  the  developing 
spleen  but  erythrocyte  formation  ceases  after  birth,  although  following  severe 
haemorrhage  the  function  may  be  resumed  even  in  adult  life.  The  formation 
of  lymphocytes,  however,  goes  on  throughout  life  in  the  splenic  corpuscles. 


FIG.  249. — From  the  liver  of  a  rabbit  embryo,  showing  formation  of  red  blood  cells.     Maximow. 
a,  Megaloblasts;  a',  megaloblast  in  mitosis;  b,  normoblasts;  c-  erythroblasts;  en,  en',  en",  endothe- 
lial  cells;   h,  liver  cells;   I,  primitive  lymphocytes;   /',  primitive  lymphocyte  in  mitosis; 
«,  nucleus  being  extruded  from  small  erythroblast. 

The  lymph  glands  are  constant  sources  of  lymphocytes,  the  parent  cells  being 
the  large  mononuclear  cells  found  in  the  germinal  centers.  These  cells  are 
regarded  as  closely  allied  to  the  primitive  lymphocytes,  perhaps  even 
identical,  although  here  in  this  particular  environment  giving  rise  only  to  the 
lymphocyte  line. 

The  bone  marrow  is  an  important  source  of  blood  cells  in  the  embryo, 
and  in  the  adult  under  normal  conditions  is  regarded  as  the  only  source  of 


272  TEXT-BOOK  OF  EMBRYOLOGY 

red  corpuscles.  The  parent  stem  cells,  here  called  myeloblasts,  are  recog- 
nizable in  the  form  of  large  mononuclear,  non-granular  cells,  with  the  general 
characters  of  primitive  lymphocytes,  which  give  rise  to  the  red  blood  cells 
through  clearly  distinguishable  megaloblast  and  normoblast  stages,  and  to 
the  various  forms  of  leucocytes  and  lymphocytes.  In  addition  the  parent 


m.  '     .W  - 


m  ^*'$j$f+ 

/  T^vi^W^^I^'     w^ 

\/S^.  V^+P'  l 

*•:     ••*V 


f  £*       ,  Jwi ,,_  0  •  ^P  ^^ 

" 

m" 


m  *      ^}       '  ^Ji  M^jf^i   ^ 

•  .^S%  .    *  ^    '     *T;"T"  m/ 

^. 

/w 


FIG.   250. — From  a  section  of  red  marrow  from  the  femur  of  a  young  rabbit.     Schdfer. 
e,  Erythrocytes;  e'.  normoblasts;  e",  normoblast  in  mitosis;  /,  outlines  of  fat  cells;  /,  polymor- 
phonuclear    leucocytes;    m,    neutrophile    myelocytes;    m',  myelocytes    in  mitosis;    m", 
eosinophile  myelocytes;  m'",  basophile  myelocytes. 

cells  also  give  rise  to  certain  other  cells  which  are  normally  confined  to  the 
marrow,  viz.,  the  myelocytes.  These  are  large  mononuclear  cells,  with 
vesicular  nuclei,  the  cytoplasm  containing  neutrophile,  acidophile,  or  baso- 
phile granules  similar  to  those  of  the  leucocyte  series  (Fig.  250).  The 
genetic  relationships  of  the  " giant"  cells,  or  myeloplaxes,  in  the  marrow  are 
not  clear.  The  myeloplaxes  are  large  masses  (30  to  100  micra  in  diameter) 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


273 


of  homogeneous  or  finely  granular,  slightly  basophilic  cytoplasm  containing 
either  a  single  tabulated,  annular  nucleus  (megakaryocytes ,  Fig.  250,  meg) 
or  many  nuclei  (polykaryocytes).  The  polykaryocytes  have  been  considered 
identical  with  the  osteoclasts,  which  may  represent  fused  osteoblasts,  but 
this  relationship  has  not  been  definitely  established.  Both  kinds  of  cells 
have  been  considered  as  derivatives  of  the  myeloblasts,  the  polykaryocytes 
being  later  stages  of  megakaryocytes. 

The  blood  platelets  are  now  regarded  by  some  authors  as  derivatives  of 
the  megakaryocytes;  pseudopodia  of  the  latter  breaking  off  and  gaining 
access  to  the  blood  stream.  By  others  they  are  not  believed  to  be  formed 
constituents  of  the  circulating  blood,  but  appear  only  after  shed  blood 
comes  in  contact  with  a  foreign  substance. 

The  accompanying  table,  which  is  a  tentative  graphic  scheme  of  the 
monophyletic  theory,  will  assist  the  student  in  tracing  the  lineage  of  the 
blood  cells. 

Primitive  lymphocyte  (Maximow) 
Primitive  blood  cell — Haemoblast 


Primitive 
blood  cell 


/ 

Lymphocytes 


Polymorph 


Granular     Non-granular 
\  l\ 


Momonuclear   \  Mononnclear 


Transitional     I  Transitional 


Neutrophile  Basophile      Basophile 
Acidophile     Neutrophile  Acidophile 
Acidophile    Neutrophile 


\ 
Megaloblast 

Normoblast 
Erythroblast 

Erythrocyie 
\ 
Megaloblast 

etc. 


Primitive 
blood  cell 


Lymphocytes 


Myelol 

Neutrophile 
myelocyte 
Acido 
myelo 

alast     Leucocyte  series 
\             (as  above) 
Basophile 
myelocyte 

plille 
cyte 

Primitive 
blood  cell 
etc. 

THE  LYMPH  VASCULAR  SYSTEM. 


A  controversy  has  arisen  over  the  origin  of  the  lymph  channels  and  their 
endothelium,  similar  to  the  one  that  arose  over  the  genesis  of  the  blood  vessels. 
There  are  therefore  two  main  views,  viz.:  (i)  that  the  endothelium  of  the 
lymph  vessels  arises  as  sprouts  from  the  endothelium  of  veins  and  continues 
to  grow  by  proliferation  and  migration  of  its  own  cells,  the  lymphatics  thus 


274 


TEXT-BOOK  OF  EMBRYOLOGY 


being  direct  derivatives  of  the  venous  channels;  (2)  that  the  lymph  vessels 
arise  in  situ  through  enlargement  and  coalescence  of  intercellular  tissue 
spaces,  the  mesenchymal  cells  bounding  these  spaces  becoming  flattened  and 
rearranged  to  form  the  endothelial  walls  of  the  vessels,  and,  as  a  corollary, 
that  the  junction  of  the  lymph  vessels  with  the  veins,  which  occurs  at  certain 
definite  points,  is  a  secondary  matter. 

Here  again  the  scope  of  the  work  does  not  permit  presentation  in  detail 


Ant.  cardinal  vein    f~ 
Subclavian  vein 

Post,  cardinal  vein  •--/-/--— — 

I 

Diaphragm-  — 


Suprarenal  gland  - 
Mesonephros- 

.  Kidney- 


Ant,  lymph  heart 

Deep  lymphatics 

of  arm 


Branches  to  heart 

Branches  to  lung 

Aorta 

Branch  to  oesophagus 

Branches  to  stomach 

Branch  to  duodenum 

Branches  to  mesenteric  plexus 
Cisterna  chyli 


Post,  lymph  heart 

Deep  lymphatics 

to  leg 

*  /        \l         ^  *  , 

FIG.  251. — Diagram  showing  the  arrangement  of  the  lymphatic  vessels  in  a 
pig  embryo  of  40  mm.     Sabin. 

of  the  evidence  adduced  in  favor  of  either  of  these  views.  The  advocates 
of  the  first  view  have  placed  much  dependence  upon  the  method  of  in- 
jection, which,  as  in  the  case  of  the  origin  of  blood  vessels,  has  been  met 
with  the  criticism  that  injection  shows  only  those  lymph  channels  with  con- 
tinuous lumina  and  leaves  undetermined  the  field  beyond  the  injected  area 
(see  page  225).  To  supplement  their  studies  by  the  injection  method,  the 
investigators  who  maintain  that  lymphatic  endothelium  grows  by  sprouting 
of  preexisting  endothelium  have  added  studies  on  living  tissues  in  which 
the  sprouting  phenomena  are  claimed  to  be  clearly  observable.  Those  who 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


275 


maintain  that  the  lymphatics  and  their  endothelium  arise  in  situ  from 
intercellular  tissue  spaces  and  the  bordering  cells,  argue  that  the  same 
principles  underlie  the  formation  of  lymphatics  that  determine  blood-vessel 
development  and  that  it  has  been  shown  experimentally  that  blood  vessels 
develop  in  regions  which  have  been  entirely  cut  off  from  any  source  of  endo- 
thelium except  the  mesenchymal  cells 
in  situ  (see  page  225). 

According  to  the  first  view  lym- 
phatic development  can  be  divided  into 
two  stages:  (i)  the  formation  of  isolated 
lymph  sacs,  derived  from  veins,  which 
become  united  into  a  system,  and  (2) 
the  peripheral  growth  of  lymph  vessels 
which  sprout  from  the  endothelium  of 
these  sacs  and  spread  through  the  body, 
(i)  The  first  sacs  appear,  one  on  each 
side,  along  the  jugular  (anterior  cardi- 
nal) veins.  The  branches  of  these  veins 
at  first  form  a  plexus;  a  portion  of  the 
plexus  becomes  cut  off  from  the  parent 
stems  and  lies  as  a  series  of  isolated 
spaces  in  the  mesenchyme ;  these  spaces 
then  enlarge  and  coalesce  to  form  an  en- 
do  thelial-lined  sac — the  jugular  lymph 
sac  or  heart — which  afterward  joins  the 
jugular  vein  by  a  new  opening  (Fig. 
251).  A  second  pair  of  sacs — the  pos- 
terior lymph  sacs  or  hearts — develops 
in  the  same  manner  from  the  more 
caudal  branches  of  the  posterior  cardi- 
nal veins  (Fig.  251).  Two  other  sac- 
like  structures  develop — the  cisterna 

chyli  and  retroperitoneal  sac — the  former  in  the  region  of  the  renal  veins 
and  the  latter  in  the  vicinity  of  the  suprarenal  bodies.  Through  the  longi- 
tudinal fusion  of  the  chain  of  sac-like  structures,  the  axial  lymphatic  drain- 
age line  of  the  body  is  established  (Fig.  251).  The  thoracic  duct  probably 
represents  the  fused  cisterna  chyli  and  jugular  lymph  hearts.  The  lymph 
hearts  in  the  avian  and  mammalian  embryo  become  relatively  smaller  as 
development  proceeds  until  in  the  adult  they  are  barely  discernible  as  slight 
dilatations  in  the  lymph  vessels.  The  cisterna  chyli,  however,  may  persist 
as  a  clearly  distinguishable  dilatation  at  the  caudal  end  of  the  thoracic  duct. 


FIG.  252. — Diagram  showing  network  of 
lymphatic  vessels  in  skin  of  pig  embryos. 
Sabin. 

Area  marked  A  shows  extent  of  network  in 
an  embryo  of  18  mm.;  B,  in  embryo  cf 
20  mm.;  C,  in  embryo  of  30  mm.;  D,  in 
embryo  of  40  mm. 


276 


TEXT-BOOK  OF   EMBRYOLOGY 


(2)  The  peripheral  lymph  channels,  which  drain  into  the  thoracic  duct, 
represent  outgrowths  from  the  lymph  sacs.     From  the  jugular  sacs  sprouts 


FIG.  253. — From  cross-sections  of  cat  embryos  in  successive  stages  (a,  b,  c,  d)  of  development, 
in  the  region  of  the  jugular  lymph  sac ;  diagrammatic  but  amply  supported  by  studies  of  serial 
sections  and  reconstructions.  Huntington. 

i,  Anterior  cardinal  vein;  2,  somatic  tributary  of  same;  4,  developing  blood  cells  in  the  mesen- 
chyme;  5,  mesenchymal  intercellular  spaces — rudiments  of  the  jugular  lymph  sac;  6,  rudi- 
ments of  brachio-cephalic  venous  anastomosis;  7,  brachio-cephalic  venous  anastomosis;  8, 
haemophoric  lymphatic  plexus — forerunner  of  jugular  lymph  sac;  n,  thoracic  duct- 
'approach'  of  jugular  lymph  sac;  12,  rudiments  of  thoracic  duct;  13,  jugular  lymph  sac  pre- 
paring to  rejoin  vein  and  to  establish  secondary  connection  with  rudiments  of  thoracic 
duct  (12)  and  of  other  systemic  lymphatics  (14);  15,  jugular  lymph  sac,  which  has  re- 
joined vein  through  permanent  lymphatico-venous  tap  (16);  17,  thoracic  duct;  18,  jugular 
and  cephalic  systemic  lymphatics. 

invade  the  neck,  head,  shoulders,  and  finally  the  entire  upper  extremities 
and  upper  part  of  the  body  wall  (Fig.  252).  Similarly,  from  the  posterior 
lymph  hearts  sprouts  invade  the  lower  extremities  and  lower  portion  of  the 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


277 


body  wall  (Fig.  252) .  Outgrowths  from  the  original  axial  drainage  line  invade 
the  various  visceral  organs  (Fig.  251).  Thus  the  lymphatic  drainage  of  the 
body  is  effected  through  outgrowths  from  a  few  primary  centers  which 
represent  derivatives  of  the  venous  channels.  The  lymph  glands  are  second- 
ary foci  of  development  along  the  lymph  vessels  (see  page  280), 

The  view  that  lymphatics  arise  as  enlarged  isolated  intercellular  spaces 
in  the  mesenchyinal  tissue  does  not  include  any  dispute  as  to  the  general 


FIG.  254. — From  a  photograph  (X  600)  of  a  cross-section  through  the  caudal  end  of    a  chick 

embryo    of    15    mm.,  showing   enlarged    mesenchymal  intercellular  spaces  as  rudiments 

of  the  posterior  lymph  sac.     West. 
3,  Coccygeal  vein;  6,  caudal  muscle  plate;  8,  isolated  enlarged  intercellular  spaces,  the  bounding 

cells  becoming  flattened;  9,  lateral  branch  of  coccygeal  vein;  10,  lymphatics  containing 

collections  of  developing  blood  cells. 

disposition  of  the  lymph  channels  in  the  body,  but  comprises  a  funda- 
mentally different  concept  of  the  origin  of  these  vessels.  Upon  a  long  and 
exhaustive  series  of  observations  on  closely  graded  series  of  embryos  of 
Fishes,  Amphibia,  Reptiles,  Birds,  and  Mammals  is  based  the  conclusion 
that  not  only  the  lymph  sacs  but  the  peripheral  lymphatics  as  well  originate 
independently  of  the  veins;  and  that  the  opening  of  the  main  lymphatic 
drainage  lines  into  the  jugular  or  subclavian  veins  near  their  junction, 


278 


TEXT-BOOK  OF  EMBRYOLOGY 


and  into  the  inferior  vena  cava  and  renal  veins  (in  some  monkeys) ,  is  second^ 
arily  established.  The  same  hydrodynamic  mechanical  factors  regarded 
as  operative  in  the  formation  of  blood  vessels,  viz.:  pressure  and  friction 
incident  to  blood  flow  (see  page  226),  are  considered  as  effective  likewise 
in  the  development  of  lymphatics.  Fundamentally,  therefore,  the  lymph 
vascular  system  from  the  viewpoint  of  development  differs  in  no  wise  from 
the  blood  vascular  system/ 


\ 


FIG.  255. — Diagrams  showing  three  stages  (a,  b,  c)  in  the  development  of  the  thoracic  duct  in 
the  cat  embryo,  in  which  the  jugular  lymph  sac  has  established  two  permanent  venous 
connections  (8  and  9).  Huntington. 

i,  Anterior  cardinal  vein;  2,  duct  of  Cuvier;  3,  posterior  cardinal  vein;  4,  external  jugular- 
cephalic  vein;  5,  subclavian  vein;  6,  jugular  lymph  sac;  7,  thoracic  duct  'approach'  of 
lymph  sac;  8,  common  jugular  opening  of  lymph  sac;  9,  jugulo-subclavian  opening  of  lymph 
sac;  10,  rudiments  of  thoracic  duct;  n,  thoracic  duct. 

The  lymph  sacs,  both  jugular  and  posterior,  arise  through  enlargement 
and  confluence  of  mesenchymal  intercellular  spaces,  the  cells  bounding  the 
spaces  becoming  flattened  and  rearranged  to  form  endothelium.  In  the 
case  of  the  mammalian  (cat)  jugular  sac,  intercellular  spaces  in  the  region 
dorso-lateral  to  the  anterior  cardinal  vein  unite  into  an  intricate  plexus  of 
channels  which  then  opens  into  the  vein  (Fig.  253,  a  and  b).  Following 
this  the  components  of  the  plexus  enlarge  and  coalesce  to  form  the  sac, 
which  then  temporarily  severs  connection  with  the  vein  (Fig.  253,  c).  Finally 
the  sac  effects  a  permanent  connection  with  the  vein  through  one  or  more 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM  279 

openings  which  represent  the  lymphatico-venous  communications  of  the 
adult  (Fig.  253,  d).  In  the  case  of  the  posterior  sac,  intercellular  spaces 
dorsal  to  the  posterior  cardinal  vein  (.Fig.  254,  8)  first  form  a  plexus  the 
components  of  which  then  unite  into  a  large  endothelial-lined  space  which 
opens  into  the  dorsal  tributaries  of  the  vein. 

The  thoracic  duct  also  arises  as  a  chain  of  isolated  endothelial-lined 
spaces  along  the  line  of  the  aorta.  These  unite  longitudinally  into  a  con- 
tinuous channel  which  joins  the  jugular  lymph  sac,  thus  forming  the  axial 
lymphatic  drainage  line  of  the  body  (Fig.  255,  a,  b,  c).  In  reptilian  embryos 
the  spaces  first  fuse  into  a  distinct  periaortic  plexus  out  of  which  the  thoracic 
duct  is  established.  In  the  avian  embryo  the  chain  of  spaces  follows  the 
general  line  of  the  aorta  but  does  not  become  so  intimately  associated  with 
the  great  arterial  trunk  as  in  reptiles.  In  the  mammalian  forms  rudiments 
of  the  thoracic  duct  follow  the  same  general  plan  of  development,  but  are 
associated  topographically  with  the  ventro-medial  tributaries  of  the  azygos 
veins.  These  tributaries  finally  become  detached  from  the  larger  venous 
trunks,  atrophy  and  disappear,  being  replaced  by  the  thoracic  duct. 

On  the  same  principles  laid  down  for  the  development  of  the  lymph  sacs 
and  thoracic  duct,  the  peripheral  lymphatics  also  are  developed.  In  all 
the  regions  of  the  body  not  immediately  drained  by  the  lymph  sacs  or 
thoracic  duct,  mesenchymal  intercellular  spaces  enlarge  and  coalesce,  the 
cells  bounding  the  coalesced  spaces  being  transformed  directly  into  endo- 
thelium;  the  spaces  unite  to  form  a  plexus  of  endothelial-lined  channels, 
and  in  this  plexus  certain  channels  increase  in  size  to  form  the  larger  lym- 
phatics which  converge  and  eventually  join  the  main  axial  drainage  line. 
Thus  the  lymphatic  drainage  of  the  entire  body  is  established. 

One  of  the  most  interesting  and  significant  phases  of  lymphatic  develop- 
ment, which  has  been  brought  out  through  recent  studies  of  the  problem,  is 
the  role  played  by  certain  early  lymph  channels  in  conveying  blood  cells  to 
the  general  circulation.  It  has  been  found  that,  in  the  region  subsequently 
occupied  by  the  lymph  sacs,  extensive  blood  cell  formation  (haemopoiesis) 
occurs  prior  to  the  formation  of  lymphatic  rudiments.  As  the  lymph  spaces 
appear  and  unite  into  a  plexus  the  developing  blood  cells  are  included  within 
them  (Fig.  253,  a  and  Fig.  254,  10).  When  the  lymphatic  plexus  joins 
the  veins  the  blood  cells  are  carried  into  the  general  circulation  (Fig.  253,  b). 
This  haemophoric  function  of  the  early  lymph  channels  is  especially  prominent 
in  the  case  of  the  thoracic  duct  in  the  chick.  Here  extensive  collections  of 
blood  cells  develop  in  the  mesenchymal  tissue  along  the  line  of  the  aorta 
and  become  included  within  the  rudiments  of  the  thoracic  duct  and  eventu- 
ally, when  the  latter  unites  with  the  jugular  lymph  sac,  are  carried  into  the 
veins  and  thus  enter  the  general  circulation.  After  these  early  lymphatics, 


280 


TEXT-BOOK  OF  EMBRYOLOGY 


which  transport  blood  cells  and  which  have  been  denned  as  haemophoric 
lymphatics,  or  veno-lymphatics,  fulfil  their  haemophoric  function  they  are 
retained  as  permanent  lymph  channels  in  the  general  lymphatic  organiza- 
tion. In  a  broader  interpretation,  the  haemophoric  function  of  certain 
lymph  vessels  during  ontogeny  is  particularly  significant  in  that  it  indicates 
essential  and  fundamental  similarity  of  lymphatic  vascular  development  to 
haemal  vascular  development. 

The  Lymph  Glands. 

The  lymph  glands  do  not  begin  to  develop  for  some  time  after  the  lym- 
phatic vessels,  since  there  are  no  indications  of  them  in  the  human  fcetus 
until  the  latter  part  of  the  third  month  and  none  in  pig  embryos  until  thev 

Efferent  lymph,  ves. 


Blood  vessel 


-ji^Marginal  sinus 
$5'*'  Capsule 


*--l!7$ 


Afferent 
lymph,  ves. 


FIG.  256. — From  a  section  through  the  axilla  of  a  human  embryo  of  125  mm.  (4-5  months), 
showing  an  early  stage  of  a  lymph  gland.     Kling. 

have  reached  a  length  of  30  mm.  While  it  is  definitely  settled  that  lymph 
glands  originate  in  very  close  relation  with  the  lymphatic  vessels,  certain 
points  in  their  later  development  need  further  study.  In  the  axilla  and 
groin,  for  example,  the  lymphatic  vessels  form  a  dense  network  in  the  meshes 
of  which  are  masses  of  connective  tissue.  These  masses  become  more 
cellular  and  with  the  surrounding  vessels  constitute  the  anlagen  of  lymph 
glands  (Fig.  256).  The  new  cells  which  appear  in  the  masses  are  lympho- 
cytes which  may  pass  through  the  walls  of  the  neighboring  blood  vessels  and 
lodge  here  or  may  be  derived  directly  from  connective  tissue  (mesenchymal) 
cells  in  situ.  Whatever  the  origin  of  the  lymphocytes  may  be,  they  have  the 
opportunity  here  to  divide  freely.  The  mass  becomes  still  more  cellular  and 
enlarges  at  the  expense  of  the  lymphatic  vessels  which  then  come  to  form  a 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM 


281 


network  around  the  mass.  This  network  is  the  marginal  plexus,  and  it 
communicates  freely  with  the  neighboring  lymphatic  channels.  Within 
the  mass  of  cells  blood  vessels  are  present  from  the  beginning,  and  these 
are  destined  to  be  the  blood  vessels  of  the  lymph  gland,  and  the  point  of  their 
entrance  and  exit  marks  the  hilus.  Outside  of  the  marginal  plexus  the  con- 
nective tissue  condenses  to  form  the  capsule.  The  gland  at  this  stage  thus 
consists  of  a  central  compact  cellular  mass,  made  up  of  connective  tissue 
and  lymphocytes,  in  which  blood  vessels  ramify;  a  plexus  of  lymphatic 
channels  around  the  mass  which  communicate  with  the  neighboring  channels ; 
and  around  the  whole  structure  a  capsule  of  connective  tissue  (Fig.  256). 
Further  development  consists  of  the  breaking  up  of  the  cell  mass  by 

Afferent  lymphatic  vessels 


Marginal  sinus 


Dense  lymph, 
tissue 


Intermediary 
plexus 


Efferent  lymph,  vessel 


Blood  vessels 


FIG.  257. — Diagram  illustrating  a  stage  (later  than  Fig.  256)  in  the  development 
of  a  lymph  gland.     Stohr. 

lymphatic  channels  and  the  formation  of  the  follicles.  It  seems  probable 
that  branches  from  the  marginal  plexus  invade  the  cell  mass  principally 
from  an  area  around  the  hilus,  thus  breaking  it  up  into  smaller  irregular 
masses  or  cords.  At  the  side  opposite  the  hilus  the  invading  channels  are  less 
numerous,  leaving  larger  parts  of  the  mass  which  become  the  follicles  (nodules) 
of  the  cortex.  On  all  sides  the  invading  channels  communicate  with  the 
marginal  plexus  and  form  the  so-called  intermediary  plexus.  The  gland  as 
a  whole  enlarges  and  its  peripheral  part  pushes  outward  into  the  surrounding 
tissue.  Over  the  follicles  the  capsule  is  pushed  outward,  while  between  them 
it  remains  in  place  and  comes  to  dip  into  the  gland  as  the  trabecula.  The 
blood  vessels  tend  to  lie  in  the  trabeculae,  but  a  small  branch  probably 
passes  to  each  follicle.  In  the  follicles  themselves  the  lymphocytes  pro- 


282  TEXT-BOOK  OF  EMBRYOLOGY 

liferate  and  the  central  part  of  each  follicle  becomes  a  germinal  center.  The 
connective  tissue  among  the  lymphatic  vessels  composing  the  marginal  plexus 
becomes  proportionately  less  as  the  vessels  enlarge  and  finally  exists  only  as 
strands  of  reticular  tissue  which,  naturally,  are  covered  by  the  endothelium ; 
thus  the  marginal  plexus  becomes  the  marginal  sinus.  The  intermediary 
sinus  is  formed  by  the  channels  which  originally  invaded  the  cell  mass.  The 
reticular  tissue  is  probably  composed  of  remnants  of  the  original  connective 
tissue.  All  the  channels  converge  at  the  hilus  to  form  the  efferent  lymphatic 
vessels  (Figs.  257  and  258). 

The  haemolymph  glands   are  probably  developed  in   much   the   same 


Afferent  lymph,  vessels 


Marginal 
plexus 


Lymph  follicle 


Medullary  cord 


Intermediary, 
nlexus 

«nvm ^«K«a  ^    ^» .  — -  *  -  «™*  -*  »**     >  Trabecula 


Capsule^  '•f\**^ 

Efferent  lymph,  vessels 

FIG.  258. — Diagram  illustrating  a  late  stage  in  the  development  of  a  lymph  gland. 
Compare  with  Fig.  257.     Stohr. 

manner  as  the  lymph  glands  except  that  in  the  former  the  sinuses  are  filled 
with  red  blood  cells. 

The  first  lymph  glands  to  develop  are  those  in  the  axilla,  in  the  inguinal 
region,  in  the  neck,  and  in  the  base  of  the  mesentery.  These  are  the  so-called 
primary  glands  and  develop  during  fcetal  life.  They  are  of  constant  occur- 
rence in  these  regions,  but  vary  in  number  in  different  individuals.  The 
secondary  lymph  glands  are  those  in  the  bend  of  the  elbow,  in  the  popliteal 
space,  in  the  mesentery,  and  around  the  aorta.  Some  of  these  develop  during 
fcetal  life  and  some  later.  While  lymph  glands  are  of  constant  occurrence  in 
some  regions  throughout  life,  the  number  may  vary  at  different  times  in  any 
region;  and  there  may  also  be  variations  in  different  individuals.  Glands 
may  be  called  into  existence  at  any  time  during  life,  in  almost  any  region, 
as  the  result  of  exceptional  activity  of  some  organ,  or  in  pathological  con- 
ditions. Such  structures  are  known  as  tertiary  lymph  glands. 


THE   DEVELOPMENT  OF  THE  VASCULAR   SYSTEM  283 

The  origin  of  the  lymph  (plasma)  itself  is  probably  extremely  complex. 
A.t  one  time  it  was  considered  as  the  result  of  nitration  from  the  blood  plasma 
through  the  capillary  walls.  If  lymph  originates  in  this  way  the  nitration 
is  selective,  for  the  chemical  composition  of  the  lymph  differs  from  that  of 
the  blood  plasma.  In  all  probability  the  lymph  plasma  consists  of  blood 
plasma  which  has  escaped  through  the  vessel  walls  plus  the  products  of  cell 
activity  in  the  tissues. 

The  Spleen. 

Since  the  spleen  is  generally  considered  as  a  lymphatic  organ  and  since 
recent  researches  have  shown  that  its  structure  is  quite  comparable  to  that 
of  the  lymph  glands,  it  seems  advisable  to  consider  it  under  the  head  of  lym- 
phatic organs.  Its  ultimate  origin  is  not  yet  settled  and  the  details  of  its 
later  development  are  still  obscure.  The  same  difficulties  are  met  with  as  in 
the  case  of  the  origin  and  development  of  blood  cells,  for  it  is  known  that  the 
spleen  plays  a  part  in  the  formation  of  the  blood  cells.  Its  structure  differs 
from  that  of  the  lymph  glands  chiefly  in  that  it  possesses  no  distinct  lym- 
phatic sinuses;  but  it  does  possess  lymph  follicles  (splenic  corpuscles)  and 
densely  cellular  cords  (pulp  cords)  which  are  separated  by  cavernous  blood 
vessels  (cavernous  veins). 

For  some  time  the  spleen  was  considered  as  a  derivative  primarily  of  the 
mesenchyme  in  the  region  of  the  dorsal  mesogastrium.  More  recently, 
however,  investigators  have  taken  the  view  that  it  arises  partly,  or  possibly 
entirely,  from  the  mesothelium  (ccelomic  epithelium)  of  the  dorsal  mesogas- 
trium. In  human  embryos  during  the  fifth  week  the  anlage  of  the  spleen 
appears  as  an  elevation  on  the  left  (dorsal)  side  of  the  mesogastrium  (Fig. 
259).  This  elevation  is  produced  by  a  local  thickening  and  vascularization 
of  the  mesenchyme,  accompanied  by  a  thickening  of  the  mesothelium 
which  covers  it;  and,  furthermore,  the  mesothelium  is  not  so  distinctly 
marked  off  from  the  mesenchyme  as  in  other  regions.  Cells  from  the 
mesothelium  then  migrate  into  the  subjacent  mesenchyme  and  the  latter 
becomes  much  more  cellular  (Fig.  260).  The  migration  is  brief,  and  in 
embryos  of  about  forty-two  days  has  ceased,  and  the  mesothelium  is  again 
reduced  to  a  single  layer  of  cells.  The  elevation  becomes  larger  and  projects 
into  the  body  cavity.  At  first  it  is  attached  to  the  mesentery  (mesogas- 
trium) by  a  broad,  thick  base,  but  as  development  proceeds  the  attachment 
becomes  relatively  smaller  and  finally  forms  only  a  narrow  band  of  tissue 
through  which  the  blood  vessels  (splenic  artery  and  vein)  pass. 

Further  development  of  the  substance  of  the  spleen  consists  of  the  break- 
ing up  of  the  cellular  mesenchymal  tissue  by  blood  vessels  and  the  formation 
of  the  splenic  corpuscles.  The  connective  tissue  trabecula,  as  well  as  the 


284 


TEXT-BOOK   OF   EMBRYOLOGY 


capsule  of  the  spleen  are  derived  from  the  original  mesenchymal  tissue.  The 
blood  vessels  become  dilated  in  parts  of  their  course  to  form  the  cavernous 
vessels  (cavernous  veins)  which  are  separated  by  the  pulp  cords.  The  con- 
nective (reticular)  tissue  of  the  pulp  cords  is  a  derivative  of  the  mesenchyme, 
as  are  also  the  various  types  of  cells  in  the  cords.  The  adventitia  of  the 
walls  of  some  of  the  small  arteries  becomes  infiltrated  with  lymphocytes  to 
form  the  splenic  corpuscles  (lymph  follicles). 

It  is  generally  recognized  that  during  fcetal  life  the  spleen  is  a  hemato- 

Aorta 


Omental 
bursa 


Right  side 


Mesonephros 


Spleen 


Dorsal 

mesogastrium 
(greater  omentum) 


Abdominal  cavity 
(coelom) 


Stomach 
Left  side 


Bile  duct        Ventral  mesogastrium 
(lesser  omentum) 

FIG.  259. — From  transverse  section  through  stomach  region  of  a  14  mm. 
pig  embryo.     Photograph. 


poietic  organ,  that  is,  both  leucocytes  and  nucleated  red  blood  cells  are  pro- 
duced within  it.  Normally,  the  formation  of  erythrocytes  stops  at  or  soon 
after  birth.  In  severe  anaemia  or  in  pernicious  anaemia  in  postnatal  life, 
however,  the  presence  of  dividing  nucleated  red  blood  cells  suggests  a  return 
to  embryonic  conditions.  The  reticular  tissue  constitutes  the  source  of  these 
nucleated  forms  (erythroblasts) .  It  has  also  been  suggested  that  the  spleen 
acts  as  a  destroyer  of  worn-out  erythrocytes,  for  in  many  cases  apparent 
remnants  of  the  latter  have  been  observed  within  the  cytoplasm  of  the 


THE  DEVELOPMENT  OT  THE  VASCULAR   SYSTEM  285 

"  spleen  cells."  The  lymphocytes  proliferate  to  a  certain  extent  in  the  splenic 
corpuscles,  and  in  that  way,  at  least,  the  spleen  serves  as  a  base  of  supply  for 
leucocytes.  There  is  a  possible  suggestion  that  the  first  leucocytes  of  the 
spleen  have  their  origin  in  the  mesenchymal  cells  of  the  spleen  anlage.  This 
would  be  in  accord  with  the  observations  which  indicate  that  leucocytes  are 
derived  from  indifferent  mesenchyme  cells. 


Mesothelium       Anlage  of  spleen 
\  / 


Mesenchyme 


-- 


FiG.  260. — From  section  through  dorsal  mesogastrium  (anlage  of  spleen)  of  a  chick  embryo 
of  3  days  and  21  hours  incubation.    Tonkoff. 

Glomus  Coccygeum. 

The  coccygeal  skein  (coccygeal  gland)  was  originally  considered  as  belong- 
ing to  the  same  category  as  the  suprarenal  glands,  but  the  latest  researches 
have  indicated  that  its  cells  do  not  possess  the  characteristic  chromafrin 
reaction  and  that  it  belongs  rather  to  the  category  of  lymph  glands.  It 
develops  ventral  to  the  apex  of  the  coccyx  in  relation  with  branches  of  the 
middle  sacral  artery. 

Although  the  thymus  gland  becomes  a  lymphatic  structure  it  is  primarily 
derived  from  the  epithelium  (entoderm)  of  the  branchial  grooves  and  will  be 
considered  in  connection  with  the  development  of  the  alimentary  tract  (Chap. 
XII).  The  tonsils  also  will  be  considered  in  the  same  connection. 

Anomalies. 

ANOMALIES  OF  THE  HEART. 

ACARDIA. — The  malformation  known  as  acardia  occurs  in  the  case  of  twins 
that  have  but  one  chorion.  The  so-called  acardiac  condition  does  not 


286  TEXT-BOOK   CF   EMBRYOLOGY 

necessarily  imply  the  absence  of  the  heart  in  the  affected  twin,  for  the  latter 
may  develop  to  a  considerable  degree  and  possess  a  functionating  heart. 
On  the  other  hand,  the  affected  twin  may  be  only  an  amorphous  mass  of 
tissue  which  derives  its  total  blood  supply  through  the  agency  of  the  stronger 
twin's  heart.  Or  there  may  be  any  intermediate  form  between  these  two 
extremes.  The  point  is  that  the  acardiac  monster  (acardiacus)  derives  its 
blood  wholly  or  in  part  through  the  agency  of  the  stronger  heart.  A  further 
discussion  of  acardiac  monsters  and  their  possible  explanation  will  be  found 
in  Chap.  XIX. 

DOUBLE  HEART. — But  one  or  two  cases  of  a  double  heart  in  a  single 
human  foetus  have  been  recorded.  In  some  of  the  lower  forms  (chick)  it 
occurs  more  frequently.  The  explanation  is  probably  to  be  found  in  the 
double  origin  of  the  heart  in  Amniotes  (p.  227). 

ANOMALOUS  POSITION  OF  THE  HEART. — Congenital  anomalies  in  the  posi- 
tion of  the  heart  are  rare.  Dextrocardia  (heart  on  the  right  side)  is  almost 
invariably  associated  with  changes  in  the  position  of  the  viscera  (see  trans- 
position of  the  viscera,  page  335).  In  the  condition  known  as  ectopia  cordis, 
the  heart,  with  the  pericardium,  protrudes  through  a  cleft  in  the  ventral 
wall  of  the  thorax,  the  cleft  being  probably  due  to  an  imperfect  fusion  of  the 
two  sides  of  the  body  wall  in  that  particular  region. 

ANOMALIES  OF  THE  SEPTA. — The  most  frequent  anomaly  in  the  atrial 
septum  is  the  persistence  of  the  foramen  ovale.  The  entire  foramen  may 
remain  patent,  or,  as  is  more  frequently  the  case,  a  smaller  opening  may 
persist  between  the  ventral  (anterior)  border  of  the  foramen  and  the  valve  of 
the  latter  (p.  234). 

The  atrial  septum  may  be  wholly  lacking,  but  this  always  occurs  in  con- 
junction with  other  defects.  It  sometimes  happens  that  the  primary  atrial 
septum  (septum  superius),  which  grows  from  the  cephalic  side  of  the  common 
chamber,  fails  to  fuse  with  the  septum  of  the  a  trio-ventricular  aperture  (p. 
234  and  Fig.  209). 

Defects  in  the  ventricular  septum  occur  less  frequently  than  in  the  atrial 
septum.  It  may  happen  that  the  cephalic  (upper)  border  of  the  ventricular 
septum  fails  to  fuse  with  the  septum  which  divides  the  aortic  trunk  and  bulb 
into  the  aorta  and  pulmonary  artery.  This  affects  the  cephalic  (upper)  part 
of  the  septum  sometimes  called  the  pars  membranacea  (p.  235  and  Fig.  212); 
and  since  the  defect  is  situated  near  the  opening  of  the  aorta  it  brings  about 
the  so-called  "origin  of  the  aorta  from  both  ventricles."  Stenosis  of  the 
pulmonary  artery  usually  accompanies  this  condition.  Rarely  is  there  a 
deficiency  in  the  caudal  (lower)  part  of  the  ventricular  septum.  Complete 
absence  of  the  ventricular  septum  may  occur,  and  along  with  it  also  an 
absence  of  the  atrial  septum,  so  that  the  heart  is  simply  two-chambered;  or 


THE  DEVELOPMENT  OF  THE  VASCULAR  SYSTEM  287 

the  single  ventricle  may  open  into  two  atria.  The  causes  of  these  defects 
are  obscure. 

ANOMALIES  OF  THE  VALVES, — There  may  be  congenital  variations  in  the 
size  and  number  of  the  atrio-ventricular  valves,  depending  upon  abnormal 
position,  fusion,  or  division  of  the  pad-like  masses  from  which  the  valves 
develop  (p.  237). 

There  may  be  also  a  greater  or  lesser  number  of  semilunar  valves  in  the 
aorta  and  pulmonary  artery.  This  irregularity  can  probably  be  referred 
back  to  an  atypical  division  of  the  aortic  trunk  and  bulb,  and  a  corresponding 
atypical  division  of  the  protuberances  which  give  rise  to  the  valves  (p.  237). 
Variations  in  the  valves  may  or  may  not  be  accompanied  by  functional  dis- 
turbances. The  congenital  diminution  in  the  number  of  valves  should  be 
distinguished  from  the  acquired,  where  chronic  endocarditis  may  cause  a 
fusion. 

ANOMALIES  OF  THE  LARGE  VASCULAR  TRUNKS. 

ANOMALIES  OF  THE  ARTERIES. — There  may  be  a  transposition  of  the  aorta 
and  pulmonary  artery.  This  results  from  an  anomalous  division  of  the  aortic 
trunk  and  bulb.  The  partition  develops  in  such  a  way  as  to  put  the  aorta  in 
communication  with  the  right  ventricle,  and  the  pulmonary  artery  with  the 
left  ventricle  (p.  235).  Or  the  aorta  and  pulmonary  artery  may  remain  in 
direct  communication  on  account  of  an  imperfect  development  of  the 
partition.  Rarely  the  two  vessels  remain  as  a  common  stem. 

Congenital  stenosis  (constriction)  of  the  pulmonary  artery  may  occur, 
accompanied  by  an  increase  in  the  size  of  the  aorta,  possibly  due  to  an  unequal 
division  of  the  aortic  trunk  and  bulb.  After  birth  little  or  no  blood  can  pass 
to  the  lungs,  and  the  result  is  a  general  damming  (stasis)  of  the  venous  blood 
with  marked  cyanosis.  This  is  at  least  one  explanation  of  the  so-called  "  blue 
babies."  Less  frequently  there  is  a  stenosis  of  the  proximal  end  of  the  aorta, 
with  excessive  size  of  the  pulmonary  artery,  also  due  to  an  unequal  division 
of  the  aortic  trunk  and  bulb  (p.  235).  These  stenoses  are  usually,  though  not 
always,  accompanied  by  defects  in  the  ventricular  septum. 

Persistence  of  the  ductus  arteriosus  may  occur  without  any  other  defect; 
but  usually  the  persistence  is  associated  with  anomalous  conditions  of  the 
aorta  and  pulmonary  artery. 

Occasionally  the  arch  of  the  aorta  is  found  on  the  right  side.  This  condi- 
tion is  due  to  the  persistence  of  the  fourth  aortic  arch  on  the  right  side  instead 
of  the  corresponding  arch  on  the  left  side;  this  is  the  normal  condition  in 
Birds.  Rarely  both  fourth  aortic  arches  persist,  which  results  in  a  double 
arch  of  the  aorta — the  normal  condition  in  Reptiles.  (Compare  Figs.  219 
and  220.) 


288  TEXT-BOOK  OF   EMBRYOLOGY 

The  dorsal  aorta,  particularly  the  abdominal  part,  is  occasionally  found  to 
consist  of  two  parallel,  imperfectly  separated  vessels — a  condition  known  as 
double  aorta.  This  anomaly  is  due  to  an  imperfect  fusion  of  the  two  primitive 
aortae  (p.  218  and  Fig.  203). 

Numerous  variations  are  met  with  in  the  larger  branches  of  the  aorta, 
many  of  which  are  explained  by  referring  them  to  embryonic  conditions. 
Especially  noteworthy  are  the  branches  from  the  arch  of  the  aorta,  since  their 
development  is  so  closely  associated  with  the  changes  in  the  aortic  arches. 
The  normal  arrangement  passing  from  the  heart,  is  innominate  artery,  left 
common  carotid  artery,  left  subclavin  artery  (see  Fig.  220). 

1.  All  these  branches  may  be  collected  into  a  single  trunk  a  condition 
characteristic  of  the  horse. 

2.  Two  branches  may  arise  from  the  arch,     (a)  The  left  common  carotid 
unites  with  the  innominate,  and  the  left  subclavian  arises  separately.     This  is 
the  normal  arrangement  among  the  apes,  and  is  probably  the  most  common 
variation  in  man.     (b)  Very  rarely  there  are  two  innominate  arteries,  each 
formed  by  the  union  of  a  common  carotid  and  subclavian — a  condition  char- 
acteristic of  Birds. 

3.  Three  branches  may  arise  from  the  arch  but  in  a  manner  differing  from 
the  normal.     Each  subclavian  arises  separately  and  the  two  common  carotids 
are  united  into  a  single  vessel.     This  arrangement  is  found  in  some  of  the 
Cetacea. 

4.  Four  vessels  may  arise  from  the  arch,     (a)  These  are,  in  order,  in- 
nominate,  left   common   carotid,   left  vertebral,   left   subclavian.     (b)  Or 
the  order  may  be  right  common  carotid,  left  common  carotid,  left  subclavian, 
right  subclavian.     In  this  case  the  proximal  part  of  the  right  subclavian  rep- 
resents the  portion  of  the  right  dorsal  aortic  root  just  cranial  to  the  bifurca- 
tion; the  fourth  arch  on  the  right  side  disappears,     (c)  Or  very  rarely  the 
order  may  be  right  subclavian,  right  common  carotid,  left  common  carotid, 
left  subclavian. 

5.  Five  branches  of  the  arch  are  rare.     In  order  they  are  right  sub- 
clavian, right  vertebral,  right  common  carotid,  left  common  carotid,  left 
subclavian. 

6.  Very  rarely  there  are  six  branches  of  the  arch;  right  subclavian,  right 
vertebral,  right  common  carotid,  left  common  carotid,  left  vertebral,  left 
subclavian. 

ANOMALIES  OF  THE  VEINS. — The  two  pulmonary  "veins  on. each  side,  more 
frequently  those  on  the  left  side,  many  unite  into  a  common  trunk  before 
opening  into  the  atrium.  This  variation  is  probably  due  to  the  fact  that  the 
absorption  of  the  originally  single  pulmonary  trunk  into  the  wall  of  the 


THE  DEVELOPMENT  OF   THE  VASCULAR   SYSTEM  289 

atrium  does  not  proceed  far  enough  to  cause  all  four  of  the  pulmonary  veins 
to  open  separately  (see  p.  236).  The  upper  (more  cephalic)  vein  on  the  right 
side  may  open  into  the  superior  vena  cava ;  or  the  upper  vein  on  the  left  side 
may  open  into  the  left  innominate  vein.  A  possible  explanation  for  this  is 
that  the  pulmonary  veins  are  formed  after  the  heart  and  other  vessels  have 
developed  to  a  considerable  degree,  and  some  of  them  may  unite  with  the 
other  vessels  instead  of  with  the  atrium. 

Occasionally  two  superior  vena  cava  are  met  with.  In  this  case  the  right 
opens  into  the  right  atrium  in  the  normal  position;  the  left  opens  into  the 
right  atrium  through  the  coronary  sinus  which  naturally  is  much  enlarged. 
This  condition  represents  a  persistence  of  the  proximal  end  of  the  left 
anterior  cardinal  vein  and  the  left  duct  of  Cuvier,  and  is  the  normal  arrange- 
ment in  many  of  the  lower  Vertebrates.  Even  with  two  venae  cavae  there 
may  be  a  small  anastomosing  branch  in  the  position  of  the  left  innominate 
vein,  which  represents  the  normal  structure  in  the  Marsupials  (see  Figs. 
232  and  233  and  p.  254).  There  are  a  few  cases  on  record  of  a  single  left 
superior  vena  cava. 

The  inferior  vena  cava  is  also  subject  to  variations  which  represent  the 
abnormal  persistence  of  certain  embryonic  vessels.  Perhaps  the  most 
striking  of  these  variations  is  the  condition  known  as  double  inferior  vena 
cava.  There  may  be  two  parallel  vessels,  of  equal  or  unequal  size,  which 
unite  at  or  above  the  level  of  the  renal  veins.  This  condition  is  to  be  ex- 
plained by  the  persistence  of  parts  of  both  posterior  cardinal  veins.  It  is 
met  with  not  infrequently  among  the  lower  Mammals,  especially  the  Mar- 
supials (see  Figs.  233  and  236). 

Rarely  the  inferior  vena  cava  opens  into  the  superior,  and  in  this  case  the 
hepatic  veins  open  directly  into  the  right  atrium.  This  anomaly  probably 
represents  a  failure  of  the  absorption  of  the  sinus  venosus  into  the  wall  of  the 
atrium  (p.  236). 

A  left  renal  vein  may  open  into  the  left  common  iliac,  which  condition 
represents  a  persistence  of  the  more  caudal  part  of  the  left  posterior  cardinal 
(Fig.  236).  This  anomaly  is  rare. 

The  azygos  vein  occasionally  presents  variations  which  are  due  to  anoma- 
lous development.  All  the  intercostal  veins  on  the  left  side  may  be  collected 
into  a  vessel  which  opens  into  the  left  innominate  vein.  There  may  be  a 
single  median  azygos  vein;  or  there  may  be  a  transposition  of  the  azygos  vein. 
It  may  be  on  the  left  side  and  open  into  the  coronary  sinus  (normal  condi- 
tions in  the  sheep  and  a  few  other  Mammals).  The  latter  condition  repre- 
sents a  persistence  of  the  more  cephalic  part  of  the  left  posterior  cardinal 
vein  (see  Figs.  233  and  234). 


290  TEXT-BOOK  OF   EMBRYOLOGY 

Space  does  not  permit  a  discussion  of  the  great  number  of  congenital 
variations  that  occur  in  the  smaller  blood  vessels,  both  arteries  and  veins. 
The  student  is  referred,  however,  to  the  more  extensive  text-books  of 
anatomy. 

References  for  Further  Study. 

BORN,  G.:  Beitrage  zur  Entwicklungsgeschichte  des  Saugetierherzens.  Archiv  f. 
mik.  Anal.,  Bd.  XXXIII,  1899. 

CLARK,  E.  R.:  Further  Observations  on  Living  Growing  Lymphatics;  their  Relation 
to  Mesenchymal  Cells.  Am.  Jour,  of  Anat.,  Vol.  XIII,  1911. 

CLARKE,  W.  C.:  Experimental  Mesothelium.     Anat.  Record,  Vol.  VIII,  1914. 

DANTSCHAKOFF,  W.:  Untersuchungen  iiber  die  Entwicklung  des  Blutes  und  Bindege- 
webes  bei  den  Vogeln.  Anat.  Hefte,  Bd.  XXXVII,  1908. 

DANCHAKOFF,  V.:  Origin  of  the  Blood  Cells.  Development  of  the  Haematopoetic 
Organs  and  Regeneration  of  the  Blood  Cells  from  the  Standpoint  of  the  Monophyletic 
School.  Anat.  Record,  Vol.  X,  No.  5,  1916. 

ETERNOD,  A.  C.  F.:  Premiers  stades  de  la  circulation  sanguine  dans  1'ceuf  et  embryon 
humain.  Anat.  Anz.,  Bd.  XV,  1899. 

His,  W.:  Anatomic  menschlicher  Embryonen.    Leipzig,  1880-1885.     With  Atlas. 

HOCHSTETTER,  F.  i  Die  Entwickelung  des  Blutgefasssystems.  In  Hertwig's  Handbuch 
der  vergleich.  und  experiment.  Entwickelungslehre.  Bd.  Ill,  Teil  II,  1901.  Contains  also 
extensive  bibliography. 

HOWELL,  W.  H.:  The  Life  History  of  the  Formed  Elements  of  the  Blood,  Especially 
the  Red  Blood-corpuscles.  Journal  of  Morph.,  Vol.  IV,  1890. 

HUNTINGTON,  G.  S.,  and  McCLURE,  C.  F.  W.:  Development  of  Postcava  and  Tribu- 
taries in  the  Domestic  Cat.  Am.  Jour,  of  Anat.,  Vol.  VI,  1907. 

HUNTINGTON,  G.  S.:  The  Phylogenetic  Relations  of  the  Lymphatic  and  Blood  Vas- 
cular Systems  in  Vetebrates.  Anat.  Record,  Vol.  IV,  1910. 

HUNTINGTON,  G.  S.:  The  Genetic  Principles  of  the  Development  of  the  Systemic  Lym- 
phatic Vessels  in  the  Mammalian  Embryo.  Anat.  Record,  Vol.  IV,  1910. 

HUNTINGTON,  G.  S.:  The  Development  of  the  Lymphatic  System  in  Reptiles.  Anat. 
Record,  Vol.  V,  1911. 

HUNTINGTON,  G.  S.:  The  Anatomy  and  Development  of  the  Systemic  Lymphatic 
Vessels  in  the  Domestic  Cat.  Memoirs  of  the  Wistar  Institute  of  Anatomy  and  Biology, 
No.  i,  1911. 

HUNTINGTON,  G.  S.:  The  Development  of  the  Mammalian  Jugular  Lymph  Sac,  of  the 
Tributary  Primitive  Ulnar  Lymphatic  and  the  Thoracic  Ducts  from  the  Viewpoint  of 

recent  Investigations  of  Lymphatic  Ontogeny, Am.  Jour,  of  Anat.,  Vol.  XVI, 

No.  3,  1914. 

KLING,  C.  A.:  Studien  iiber  die  Entwicklung  der  Lymphdriisen  beim  Menschen. 
Archiv  f.  mik.  Anat.,  Bd.  LXIII,  1904. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen,  Bd.  II,  1907. 

LEHMAN,  H.:  On  the  Embryonic  History  of  the  Aortic  Arches  in  Mammals1.  Anat. 
Anz.,  Bd.  XXVI,  1905. 

LEWIS,  F.  T.:  The  Development  of  the  Vena  Cava  Inferior.  Am.  Jour,  of  Anat., 
Vol.  I,  1902. 

LEWIS,  F.  T. :  The  Development  of  the  Veins  in  the  Limbs  of  Rabbit  Embryos.  Am. 
Jour,  of  Anat.,  Vol.  V,  1906. 


THE  DEVELOPMENT  OF  THE  VASCULAR   SYSTEM  291 

MALL,  F.  P. :  Development  of  the  Internal  Mammary  and  Deep  Epigastric  Arteries 
in  Man.  Johns  Hopkins  Hosp.  Bull.,  1898. 

MALL,  F.  P.:  On  the  Development  of  the  Blood  Vessels  of  the  Brain  in  the  Human 
Embryo.  Am.  Jour,  of  Anat.,  Vol.  IV,  1905. 

MAXIMOW,  A. :  Die  Friihesten  Entwicklungsstadien  der  Blut-  und  Bindegewebszellen 
beim  Saugetierembryo,  bis  zum  Anfang  der  Blutbildung  in  der  Leber.  Arch.f.  mik.  Anat.t 
Bd.  LXXIII,  1909. 

MAXIMOW,  A.:  Lymphozyt  als  gemeinsame  Stammzelle  der  verschiedenen  Blutele- 
mente  in  der  embryonalen  Entwicklung  und  im  postfetalen  Leber  der  Saugetiere.  Folia 
Hamatolog.,  Bd.  VIII,  1909. 

MAXIMOW,  A.:  Die  embryonale  Histogenese  des  Knochenmarks  der  Saugetiere. 
Arch.  f.  mik.  Anat.,  Bd.  LXXVI,  1910. 

McCLURE,  C.  F.  W.:  The  Development  of  the  Lymphatic  System  in  Fishes  with 
Especial  Reference  to  its  Development  in  the  Trout.  Memoirs  of  the  Wistar  Institute  of 
Anatomy  and  Biology,  No.  4,  1915.  ^ 

McCLURE,  C.  F.  W.,  and  SILVESTER,  C.  F.:  A  Comparative  Study  of  the  Lymphati- 
co- Venous  Communications  in  Adult  Mammals.  Anat.  Record,  Vol.  Ill,  1909. 

MILLER,  A.  M.:  Histogenesis  and  Morphogenesis  of  the  Thoracic  Duct  in  the  Chick;; 
Development  of  Blood  Cells  and  their  Passage  to  the  Blood  Stream  via  the  Thoracic 
Duct.  Am.  Jour,  of  Anat.,  Vol.  XV,  1913. 

MIXOT,  C.  S.:  On  a  Hitherto  Unrecognized  Form  of  Blood  Circulation  without  Capil- 
laries in  the  Organs  of  Vertebrata.  Proc.  Boston  Soc.  Nat.  Hist.,  Vol.  XXIX,  1900, 

ROSE,  C.:  Zur  Entwickelungsgeschichte  des  Saugetierherzens.  Morph.  Jahrbuch,  Bd. 
XV,  1889. 

RUCKERT,  J.,  and  MOLLIER,  S.:  Die  erste  Entstehung  der  Gefasse  und  des  Blutes  bei 
Wirbeltiere.  In  Hertwig's  Handbuch  der  vergleich  und  experiment.  Entwickelungslehre> 
Bd.  I,  Teil  I,  1906.  Contains  also  extensive  bibliography. 

SABIN,  F.  R. :  On  the  Origin  of  the  Lymphatic  System  from  the  Veins  and  the  Develop- 
ment of  the  Lymph  Hearts  and  Thoracic  Duct  in  the  Pig.  Am.  Jour,  of  Anat.,  Vol. 
I,  1902. 

SABIN,  F.  R. :  The  Origin  and  Development  of  the  Lymphatic  System.  The  Johns 
Hopkins  Hospital  Reports  Monographs,  New  Series,  No.  5,  1913. 

SALA,  L.:  Svilluppo  dei  cuori  linfatici  e  dei  dotti  toracici  nelP  embrione  di  polio. 
Ricerche  fatte  nel  laboratorio  de  anatomia  normale  della  R.  Universita  di  Roma,  Vol.  VII, 
1900. 

SCHULTE,  H.  VON  W.:  Early  Stages  of  Vasculogenesis  in  the  Cat  (Felis  domestica) 
with  Especial  Reference  to  the  Mesenchymal  Origin  of  Endothelium.  Memoirs  of  the 
Wistar  Institute  of  Anatomy  and  Biology,  No.  3,  1914. 

STOCKARD,  CHAS.  R.:  The  Origin  of  Blood  and  Vascular  Endothelium  in  Embryos 
without  a  Circulation  of  the  Blood  and  in  the  Normal  Embryo.  Am.  Jour,  of  Anat., 
Vol.  XVIII,  No.  2,  1915. 

STOERK,  O.:  tlber  die  Chromreaktion  der  Glandula  coccygea  und  die  Beziehung 
dieser  Druse  zum  Nervus  sympthathicus.  Arch.  f.  mik.  Anat.,  Bd.  LXIX,  1906. 

STOHR,  P.:  tjber  die  Entwicklung  der  Darmlymphknotchen  und  iiber  die  Riickbildung 
von  Darmdrusen.  Arch.  f.  mik.  Anat.,  Bd.  LI,  1898. 

TAXDLER,  J.:  Zur  Entwickelungsgeschichte  der  menschlichen  Darmarterien.  Anat. 
Heft,  Bd.  XXIII,  1903. 

TOXKOFF,  W.:  Die  Entwickelung  der  Milz  bei  den  Amnioten.  Archiv  f.  mik.  Anat.t 
Bd.  LVI,  1900. 


292  TEXT-BOOK  OF  EMBRYOLOGY 

WEIDENREICH,  F. :  Die  Morphologic  der  Blutzellen  und  ihre  Beziehungen  zu  einander. 
Anat.  Record,  Vol.  IV,  1910. 

WEST,  R.:  The  Origin  and  Early  Development  of  the  Posterior  Lymph  Heart  in  the 
Chick.  Am.  Jour,  of  Anat.,  Vol.  XVII,  1915. 

WRIGHT,  J.  H.:  The  Origin  and  Nature  of  the  Blood  Plates.  Boston  Med.  and  Surg. 
Jour.,  Vol.  CLIV,  1906. 


CHAPTER  XI 
THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 

Anatomy  and  Histology  show  that  there  are,  in  a  sense,  two  muscular 
systems  in  the  body,  and  Embryology  teaches  that  the  two  systems  have  dif- 
ferent origins. 

1.  The  skeletal  musculature. — This,  as  the  name  indicates,  is  closely  associated 
with  the  skeletal  system.     It  is  made  up  of  striated  muscle  fibers  arranged  to 
form  definite  bundles  or  muscles.     The  skeletal   musculature  is  under  the 
voluntary  control  of  the  central  nervous  system. 

2.  The  visceral  musculature. — This  is  found  in  connection  with  and  forms 
integral  parts  of  certain  organs.     It  is  made  up  of  two  different  kinds  of  fibers — • 
smooth  muscle  fibers  or  cells  and  striated  fibers  or  cells  (heart-muscle  cells). 
The  latter  are  found  only  in  the  wall  of  the  heart.     The  visceral  musculature  is 
involuntary,  being  under  the  control  of  the  sympathetic  nervous  system. 

Both  systems  are  derived  from  mesoderm  but  from  distinct  parts  of  the 
mesoderm.  Furthermore,  their  developmental  histories  are  quite  different,  as 
will  be  seen  in  the  following  paragraphs. 

THE  SKELETAL  MUSCULATURE. 

In  the  chapter  on  the  development  of  the  germ  layers  it  was  said  (p.  72) 
that  throughout  the  length  of  the  body  region  of  the  embryo  the  mesoderm  on 
each  side  of  the  neural  tube  and  notochord  becomes  divided  into  a  definite 
number  of  segments — the  primitive  segments  or  mesodermic  somites  (Figs.  57, 
72,  74).  These  indicate  the  segmentation  of  the  body,  and  the  history  of  the 
greater  part  of  the  skeletal  musculature  dates  from  their  differentiation  from 
the  axial  mesoderm.  Thus  the  skeletal  musculature  is,  for  the  most  part, 
primarily  segmental  in  character. 

At  first  the  primitive  segments  are  composed  of  closely  packed,  epithelial- 
like  cells,  and  each  segment  contains  a  small  cavity  which  represents  a  portion 
of  the  coelom  (Fig.  141).  The  ventro-medial  parts  of  the  segments  become 
differentiated  to  form  the  sclerotomes  which  are  composed  of  more  loosely  ar- 
ranged cells  (Fig.  261),  and  which  are  destined  to  give  rise  to  the  vertebrae  and 
to  the  various  kinds  of  connective  tissue  in  their  neighborhood.  The  lateral 
parts  of  the  segments  become  differentiated  to  form  the  cutis  plates  which  are 
destined  to  give  rise  to  a  part  of  the  corium  of  the  skin.  The  remaining  portions 

293 


294 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  the  segments  form  the  muscle  plates  or  myotomes  (Fig.  261),  from  which 
develop  by  far  the  greater  part,  at  least,  of  the  voluntary  striated  muscles. 

The  differentiation  of  the  parts  of  the  primitive  segments  begins  in  the  cervi- 
cal region  by  the  end  of  the  second  week,  and  then  gradually  proceeds  toward 
the  tail.  Three  myotomes  are  also  probably  formed  in  the  occipital  region. 
The  cells  of  the  myotomes  are  at  first  of  an  epithelial  character  (Fig.  143). 
Contractile  fibrils  appear  in  the  cells  and  the  latter  are  transformed  directly 
into  muscle  fibers.  (For  histogenesis  see  p.  307).  The  fibers  later  alter  their 
direction  in  accordance  with  the  particular  muscle  to  which  they  belong.  The 
muscle  tissue  first  formed  is  thus  segmented,  being  derived  from  the  segmen- 


Neural  crest 


Myotome 


Myotomex 
Scl. 


''    '  '— «r>>v  sg£-JX—    Sclerotome 

*Z t~" *  ''.r  *. *«r*».v 

W¥M$k 


Pronephros 

^ 

Parietal  mesoderm-- 
Intestine 


""limb  bud 


—  Amnion 


Visceral  mesoderm — - 


FIG.  261.— Transverse  section  of  human  embryo  of  the  3rd  week.     Sc/.1,  Break  in  myotome  at 
point  where  sclerotome  is  closely  attached.     Kollmann. 

tally  arranged  myotomes,  but  as  development  proceeds  the  myotomes  undergo 
extensive  changes  by  which  the  segmental  character  is  lost  in  the  majority  of 
cases.  It  is  retained,  however,  in  a  few  instances,  such  for  example  as  the 
intercostal  muscles.  The  course  of  the  changes  which  obliterate  the  segmental 
character  of  the  myotomes  and  give  rise  to  the  various  muscles  has  not  been 
observed  in  all  cases.  But  since  a  nerve  belonging  to  any  particular  segment 
and  innervating  the  myotome  of  that  segment  always  innervates  the  muscles 
derived  from  that  myotome,  it  is  possible  to  learn  something  of  the  history  of 
the  myotomes  by  studying  the  innervation  of  the  muscles. 

From  a  consideration  of  what  is  known  concerning  the  individual  histories 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM.  295 

of  the  muscles  and  concerning  the  innervation  of  the  muscles,  certain  factors 
can  be  recognized,  to  one  or  more  of  which  the  changes  in  the  myotomes  may 
be  referred.  These  factors  are  as  follows: 

1.  Migration. — The  myotomes  may  migrate  in  whole  or  in  part,  and  the 
muscles  derived  from  them  may  be  situated  far  beyond  their  limits.    For 
example,  the  latissimus  dorsi  is  derived  from  cervical  myotomes  but  ultimately 
becomes  attached  to  the  lumbar  vertebrae  and  to  the  crest  of  the  ilium.     To  this 
factor,  possibly  more  than  to  any  other,  is  due  the  loss  of  the  segmental  character 
in  the  musculature. 

2.  Fusion. — Portions  of  two  or  more  myotomes  may  fuse  to  form  one  muscle. 
For  example,  each  oblique  abdominal  muscle  is  derived  from  several  thoracic 
myotomes. 

3.  Longitudinal  Splitting. — Very  frequently  a  myotome  or  a  developing 
muscle  splits  longitudinally  into  two  or  more  portions.     The  sternohyoid  and 
the  omohyoid,  for  example,  are  formed  in  this  manner. 

4.  Tangential  Splitting. — A  developing  muscle  may  split  tangentially  into 
two  or  more  plates  or  layers.     The  two  oblique  and  the  transverse  abdominal 
muscles,  for  example,  are  formed  in  this  way. 

5.  Degeneration. — Myotomes  may  degenerate  as  a  whole  or  in  part  and  be 
converted  into  some  form  of  connective  tissue,  such  as  fascia,  ligament  or 
aponeurosis.     The   aponeuroses   of   the   transverse  and  oblique  abdominal 
muscles  are  probably  due  to  a  degeneration  of  portions  of  the  myotomes  from 
which  the  muscles  are  derived. 

6.  Change  of  Direction. — The  muscle  fibers  may  change  their  direction. 
As  a  matter  of  fact,  the  fibers  of  very  few  muscles  retain  their  original  direction. 

Muscles  of  the  Trunk. 

The  myotomes  are  at  first  arranged  serially  along  each  side  of  the  notochord  and 
spinal  cord  (compare  Fig.  262  with  Figs.  143  and  261) .  By  the  end  of  the  second 
week  fourteen  myotomes  are  differentiated  in  the  human  embryo.  Differen- 
tiation continues  until,  by  the  end  of  the  fourth  week,  the  total  number — thirty- 
eight — is  present.  Of  the  thirty-eight,  three  are  occipital,  eight  cervical,  twelve 
thoracic,  five  lumbar,  five  sacral,  and  five  (or  six)  coccygeal.  The  occipital 
myotomes  are  transient  structures  that  appear  in  relation  with  the  hypoglossal 
(XII)  nerve.  The  cervical,  thoracic,  lumbar,  sacral  and  coccygeal  myotomes 
correspond  individually  to  the  spinal  nerves  (Fig.  262).  As  stated  on  page  180, 
the  myotomes  alternate  with  the  anlagen  of  the  vertebrae.  Consequently  in  the 
cervical  region  there  are  eight  myotomes,  corresponding  to  the  eight  cervical 
spinal  nerves,  and  only  seven  vertebrae.  The  myotomes  in  the  neck  and  body 
regions  are  destined  to  give  rise  to  the  dorsal  musculature,  to  the  thoraco- 


296  TEXT-BOOK  OF  EMBRYOLOGY. 

abdominal  musculature,  to  a  part  of  the  muscles  of  the  neck,  and  to  the 
muscles  of  the  tail  region.  There  is  a  possibility  that  they  give  rise  also  to  the 
muscles  of  the  tongue. 

As  the  myotomes  continue  to  develop,  they  become  elongated  in  a  ventral 


FIG.  262. — Lateral  view  of  human  embryo  of  9  mm.  (4^  weeks).     Bardeen  and  Lewis. 

The  area  from  which  the  skin  has  been  removed  is  drawn  from  reconstructions.  The  myotomes 
have  fused  to  a  certain  extent,  so  that  segmentation  is  becoming  less  distinct.  Note  that  the 
myotomes  correspond  to  the  spinal  nerves.  The  developing  muscle  mass  (the  myotomes 
collectively)  extends  ventrally  in  the  body  wall  in  the  thoracic  region,  and  is  divided  by  a 
longitudinal  groove  into  two  parts— a  dorsal  and  a  ventro-lateral  (see  text). 

In  the  region  of  the  upper  extremity,  dense  masses  of  "  premuscle  "  tissue  are  represented  which 
later  form  the  muscles.  In  the  region  of  the  forearm  and  hand  the  "  premuscle  "  tissue  has 
been  removed  to  disclose  the  anlagen  of  the  skeletal  elements  (radius,  ulna,  and  hand  plate). 
In  the  region  of  the  lower  extremity  the  superficial  tissue  has  been  removed  to  disclose  the 
border  vien,  the  anlagen  of  the  os  coxae,  and  the  lumbo-sacral  nerve  plexus. 

direction.  Those  of  the  thoracic  region  extend  into  the  connective  tissue  of 
the  somatopleure,  or  in  other  words,  into  the  lateral  body  walls  (compare 
Figs.  262  and  263).  During  the  fifth  week  the  myotomes  give  rise  to  a  dorso- 
ventral  mass  of  developing  muscle  tissue,  in  which  the  segmental  character 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


297 


Spinal  ganglion .../; 


Dorsal  musculature 


Ventro-lateral 
musculature 


>^  Vertebral  arch 
Dorsal  ramus  of 
spinal  nerve 


Segmental  artery 

Costal  process 

Lat.  branch  of 
spinal  nerve 

Vent,  branch  of 
spinal  nerve 


FIG.  263. — Diagrammatic  cross  section  through  the  5th-6th  thoracic  segments  of  a  human  embryo 
of  9  mm.  (4^  weeks).     Bardeen  and  Lewis. 


FIG.  264. — Drawing  from  a  reconstruction  of  the  region  of  the  lower  extremity  of  a  human  embryo 
of  9  mm.  (4^  weeks).  Bardeen  and  Lewis. 

The  visceral  organs  and  the  greater  part  of  the  left  body  wall  have  been  removed.  The  8th  thoracic 
to  the  5th  sacral  segments  are  shown.  On  the  right  side  of  the  body  the  costal  processes, 
the  spinal  nerves  (including  the  lumbo-sacral  plexus),  and  the  lower  extremity  are  shown. 
On  the  left  side  the  costal  processes,  the  spinal  nerves,  and  the  nth  and  i2th  thoracic  myo- 
tomes  are  represented.  Note  the  dorsal,  lateral,  and  sympathetic  branches  of  the  spinal 
nerves. 


298 


TEXT-BOOK  OF  EMBRYOLOGY. 


largely  disappears.     The  muscle  mass  then  becomes  divided  longitudinally 
into  two  parts,  (i)  a  dorsal  and  (2)  a  ventro-lateral  (Figs.  262,  263  and  264). 

1.  The  dorsal  part  is  destined  to  give  rise  to  those  dorsal  muscles  of  the 
trunk  that  are  not  associated  with  the  extremities,  and  is  innervated  by  the 
dorsal  rami  of  the  spinal  nerves  (Fig.  263). 

2.  The  ventro-lateral  part  again  divides  longitudinally  into  (a)  a  lateral 


External  oblique 

External  inteicostal 

Internal  intercostal     I  Ventro-lateral 

Internal  oblique  |  musculature 

Transversalis 

Rectus 


FIG.  265. — Diagrammatic  cross  section  through  the  6th-yth  thoracic  segments  of  a  human  embryo 
of  17  mm.  (5^  weeks).     Bardeen  and  Lewis. 

and  (b)  a  ventral  part,  although  the  line  of   division  is  not  so  distinct  as 
between  the  original  (i)  dorsal  and  (2)  ventro-lateral  parts  (Fig.  265). 

(a)  The  lateral  part  subdivides  tangentially  and  gives  rise  in  the  cervical 
region  to  the  longus  capitis,  longus  colli,  rectus  capitis  anterior,  to  the 
scaleni,  and  to  parts  of  the  trapezius  and  sternomastoideus  (Figs.  266 
and  267).  In  the  thoracic  region  it  gives  rise  to  the  intercostales 
and  to  the  transversus  thoracis  (Figs.  265  and  268) ;  in  the  abdominal 
region  to  the  psoas,  quadratus  lumborum,  and  to  the  obliqui  and 
transversus  abdominis  (Figs.  267  and  268). 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM.  299 

(b)  The  ventral  part  gives  rise  in  the  cervical  region  to  the  sternohyoideus, 
omohyoideus,  sternothyreoideus  and  geniohyoideus.  In  the  abdominal 
region  the  ventral  part  gives  rise  to  the  rectus  abdominis  and  to  the 
pyramid  alls  (Figs.  265  and  267).  In  the  thoracic  region  there  are  no 
muscles  derived  from  the  ventral  part,  corresponding  to  those  in  the 
abdominal  region.  This  is  probably  due  to  the  development  of  the 
sternum. 


FIG.  266. — Lateral  view  of  a  human  embryo  of  u  mm.  (about  5  weeks).  Bardeen  and  Lewis. 
The  area  from  which  the  skin  has  been  removed  is  drawn  from  reconstructions.  The  dorsal  mus- 
culature has  been  removed  from  the  region  of  the  upper  extremity,  exposing  the  4th  to  the 
8th  cervical  and  the  ist  to  the  3d  thoracic  vertebrae.  The  dorsal  musculature  has  likewise 
been  removed  from  the  5th  lumbar  and  first  three  sacral  segments.  Segmentation  is  practi- 
cally lost  in  the  dorsal  musculature  in  the  thoracic  region,  but  is  still  evident  in  the  lumbar, 
sacral  and  coccygeal  regions.  The  ventro-lateral  musculature  is  distinctly  separated  from  the 
dorsal,  and  is  beginning  to  differentiate  into  the  muscles  of  the  thorax  and  abdomen. 

The  ventro-lateral  portions  of  the  lumbar  myotomes  and  of  the  first  two 
sacral  myotomes,  corresponding  to  the  ventro-lateral  portions  of  the  thoracic 
myotomes,  apparently  do  not  take  part  in  the  production  of  muscles  wrhich  be- 
long to  the  body  wall  proper.  It  is  even  questionable  whether  they  give  rise  to 
any  muscles  of  the  lower  extremities.  The  ventro-lateral  portions  of  the  third 


300  TEXT-BOOK  OF  EMBRYOLOGY. 

and  fourth  sacral  myotomes  give  rise  to  the  levator  ani,  the  coccygeus,  the 
sphincter  ani  eocternus  and  the  perineal  muscles.  The  dorsal  parts  of  the  myo- 
tomes as  far  as  the  fifth  sacral  probably  give  rise  to  the  sacrospinalis  (Fig.  266). 
THE  DIAPHRAGM. — In  addition  to  certain  structures  which  are  considered 
in  connection  with  the  pericardium  (parietal  mesoderm,  mesocardium  and 
common  mesentery — Chapter  XIV),  two  myotomes  on  each  side  enter  into 


FIG.  267. — Drawing  from  a  reconstruction  of  a  human  embryo  of  20  mm.  (about  7  weeks). 

Bardeen  and  Lewis. 

The  superficial  tissues  have  been  removed  from  the  extremities,  the  body  wall,  and  the  back. 

the  formation  of  the  diaphragm.  These  are  the  third  and  fourth  cervical  myo- 
tomes, parts  of  which  grow  into  the  developing  diaphragm  in  the  earlier  stages 
when  it  is  situated  far  forward  in  the  cervical  region  (p.  378  and  Fig.  336),  and 
give  rise  to  its  muscular  elements. 

Muscles  of  the  Head. 

Primitive  segments  (mesodermic  somites)  are  not  clearly  demonstrable  in 
the  heads  of  human  embryos,  nor,  in  fact,  in  the  heads  of  any  of  the  higher 
Vertebrates.  In  some  of  the  lower  forms,  however,  they  are  very  distinct.  It 
seems  possible,  even  probable,  that  their  indistinctness  in  the  higher  animals 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


301 


is  due  to  an  abbreviation  or  condensation  in  the  development  of  the  head 
region.  Such  condensations  are  known  to  occur  in  the  development  of  other 
structures.  In  a  human  embryo  3.5  mm.  long,  three  structures  resembling 
segments  have  been  seen  somewhat  caudal  to  the  region  of  the  ootic  vesicle  on 


FIG.  268. — Drawing  from  a  reconstruction  of  the  right  side  of  a  human  embryo  of  20  mm.  (about 

7  weeks).  Bardeen  and  Lewis. 

The  left  body  wall  and  viscera  have  been  removed.  Note  especially  the  following  muscles:  The 
deltoid  and  biceps,  just  to  the  left  of  the  brachial  plexus  and  below  the  clavicle;  the  internal 
intercostals;  the  diaphragm,  attached  to  the  body  wall;  the  transverse  abdominal  and  the 
rectus  abdominis;  the  quadratus  lumborum,  just  to  the  right  of  the  transverse  abdominal; 
the  psoas,  cut  just  above  the  lumbo-sacral  plexus;  the  levator  ani,  running  obliquely  upward 
from  the  coccygeal  region. 


one  side.  On  the  other  side  there  were  seven  similar  but  smaller  structures. 
All  were  composed  of  epithelial-like  cells  surrounding  small  cavities. 
Whether  these  segment-like  structures  bear  any  relation  to  the  mesenchymal 
condensations  which  appear  regularly  in  the  occipital  region  (p.  189),  seems 
not  to  have  been  determined. 


302 


TEXT-BOOK  OF  EMBRYOLOGY. 


Although  the  transformation  of  head  segments  into  muscles  has  not  been 
followed  in  detail  in  mammalian  embryos,  it  may  be  inferred  from  the  study  of 
lower  forms  that  three  segments  are  involved  in  the  formation  of  the  eye  muscles. 
The  most  cephalic  (anterior)  segment  gives  rise  to  the  recti  superior,  inferior 
and  medialis  (internus)  and  to  the  obliquus  inferior ,  all  of  which  are  innervated 
by  the  occulomotor  (III)  nerve.  The  next  segment  gives  rise  to  the  obliquus 
superior  which  is  innervated  by  the  pathetic  (IV)  nerve.  The  most  caudal 
segment  gives  rise  to  the  rectus  lateralis  (externus)  which  is  innervated  by  the 
abducens  (VI)  nerve. 

The  development  and  innervation  of  the  other  muscles  of  the  head  and  of 
the  hyoid  musculature  present  certain  peculiarities  which  have  caused  these 
muscles  to  be  considered  as  more  closely  related  to  the  visceral  musculature 
than  to  the  myotomic  musculature.  In  the  first  place  they  are  derived  from 


Eighth  cervical 
myotome 


Upper  limb 
bud 


Somatcpleure 

Mesonephric 
duct 


FIG.  269. — Transverse  section  through  the  eighth  cervical  segment  of  a  human 
embryo  of  2.1  mm.     Lewis. 


the  branchial  arches  (hence  are  often  called  branchiomeric  muscles},  and  not 
directly  from  the  myotomes  of  the  neck  region.  This  places  them  in  closer 
relation  to  the  visceral  muscles,  although  they  are  structurally  and  functionally 
different  from  the  latter.  In  the  second  place  the  nerves  which  supply  them 
are  fundamentally  different  from  those  which  supply  the  myotomic  muscles 
(Chap.  XVII). 

The  first  branchial  arch  on  each  side  gives  rise  to  the  temporalis,  masseter 
and  pterygoidei,  to  the  mylohyoideus  and  digastricus  (venter  anterior)  and  to  the 
tensor  tympani  and  tensor  veli  palatini.  All  these  muscles  are  innervated  by  the 
trigeminal  (V)  nerve. 

The  second  arch,  which  is  often  called  the  hyoid  arch,  gives  rise  to  a  large 
sheet  of  myogenic  tissue  which  produces  many  of  the  facial  muscles,  such  as  the 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM.  303 

platysma  and  epicranius,  the  muscles  of  expression — quadratus  labii  superioris, 
risorius,  triangularis,  mentalis,  etc.;  also  two  muscles  connected  with  the  hyoid 
bone — digastricus  (venter  posterior)  and  stylohyoideus — and  the  stapedius  of  the 
middle  ear.  The  facial  (VII)  nerve  corresponds  to  the  second  arch  and  sup- 
plies all  these  muscles. 

The  glossopharyngeal  (IX)  nerve  corresponds  to  the  third  branchial  arch, 
and  this  fact  indicates  the  muscles  derived  from  that  arch.  Some,  at  least,  of 
the  constrictor  muscles  of  the  pharynx  are  derived  from  the  third  arch.  The 
stylo-pharyngeus  is  also  a  derivative  of  the  same  arch. 

The  vagus  (X)  nerve  is  associated  with  the  fourth  and  fifth  arches  and  con- 
sequently innervates  the  muscles  derived  from  these  arches,  viz.,  the  rest  of  the 
constrictors  of  the  pharynx  (see  above),  the  laryngeal  muscles  and  the  muscles 
of  the  soft  palate  (except  the  tensor  veli  palatini  which  is  derived  from  the  first 
arch  (p.  302) .  The  glossopalatinus  and  chondroglossus  are  also  derived  from 
the  fourth  and  fifth  arches,  while  the  rest  of  the  extrinsic  muscles  of  the  tongue 
are  of  myotomic  origin. 

Two  other  muscles  are  probably  derived  in  part  from  the  branchial  arches, 
for  fibers  of  the  spinal  accessory  (XI)  nerve  afford  a  part  of  their  innervation. 
These  are  the  trapezius  and  the  sternomastoideus,  the  remaining  parts  of  which 
are  of  myotomic  origin  (p.  298). 

Muscles  of  the  Extremities. 

The  question  as  to  whether  the  muscles  of  the  extremities  are  derivatives  of 
the  myotomes  or  of  the  mesenchymal  tissue  in  the  limb  buds  has  not  been 
settled.  In  some  of  the  lower  Vertebrates,  especially  in  some  of  the  Fishes,  it 
seems  to  have  been  pretty  clearly  demonstrated  that  bud-like  processes  from 
the  myotomes  grow  into  the  anlagen  of  the  extremities  (fins),  and  there  give 
rise  to  muscles.  In  other  lower  forms  no  such  buds  from  the  myotomes  have 
been  demonstrated,  but  the  muscles  are  apparently  derived  directly  from 
the  mesenchymal  tissue  in  the  anlagen  of  the  extremities.  In  the  higher  verte- 
brates, especially  in  Mammals,  no  distinct  myotome  buds  have  been  traced  into 
the  extremities.  Some  investigators  hold,  however,  that  instead  of  myotome 
buds  some  cells  from  the  myotomes — myoblasts — wander  into  the  limb  buds 
and  give  rise  to  muscles.  Other  investigators  are  inclined  to  the  view  that  the 
musculature  of  the  extremities  is  not  of  myotomic  origin,  but  that  it  is  derived 
from  the  mesenchymal  tissue  of  the  limb  buds. 

A  most  striking  feature  of  the  musculature  of  the  extremities  is  its  distinctly 
segmental  nerve  supply.  This,  of  course,  is  in  favor  of,  although  it  does  not 
prove,  its  myotomic  origin.  If  the  muscles  of  the  extremities  are  of  myotomic 
origin,  it  is  very  probable  that  several  myotomes  take  part  in  their  formation. 


304  TEXT-BOOK  OF  EMBRYOLOGY. 

In  the  first  place  among  the  lower  Vertebrates  the  muscles  of  each  extremity  are 
derived  from  several  myotomes  and  are  innervated  by  segmental  nerves  cor- 
responding to  these  myotomes.  In  the  second  place  among  the  higher  Verte- 
brates, although  the  myotomic  origin  of  the  muscles  has  not  been  clearly  demon- 
strated, the  nerve  supply  in  each  extremity  comes  through  several  segmental 
spinal  nerves. 

Knowledge  concerning  the  development  of  the  individual  muscles  of  the  ex- 
tremities in  the  human  embryo  is  incomplete.  Especially  is  this  true  of  the 
muscles  of  the  lower  extremities. 

The  upper  limb  bud  first  appears  in  embryos  of  2-3  mm.  (during  the  third 
week)  as  a  slight  swelling  ventro-lateral  to  the  myotomes  in  the  lower  cervical 


Eighth  cervical     /„ 

myotome  /,".' 


Upper  limb  bud 


Border  vein 


FIG.  270. — Transverse  section  through  the  eighth  cervical  segment  of  a  human 
embryo  of  4.5  mm.     Lewis. 

region  (Fig.  269;  see  also  Fig.  123).  The  swelling  gradually  enlarges  and  by 
the  time  the  embryo  has  reached  a  length  of  4-5  mm.  lies  op'posite  the  last  four 
cervical  and  the  first  thoracic  myotomes.  At  this  time  it  is  filled  with  closely 
packed  mesenchymal  cells.  No  buds  from  the  myotomes  can  be  seen  extending 
into  the  mesenchyme  (Fig.  270). 

In  succeeding  stages  the  limb  bud  enlarges  still  more,  and  the  mesenchymal 
tissue  becomes  denser  (Figs.  271  and  272).  During  these  stages  no  growths, 
either  of  buds  or  of  individual  cells,  from  the  myotomes  are  apparent.  Some 
of  the  cervical  nerves,  however,  enter  the  limb  buds  (Fig.  272). 

Apparently  the  tissue  from  which  the  muscles,  as  well  as  the  skeletal  ele- 
ments, are  to  develop,  is  the  condensed  mesenchymal  tissue.  The  first  indica- 
tion of  differentiation  occurs  during  the  fourth  week  (embryo  of  about  8  mm.). 
The  central  portion  or  core  of  the  mesenchymal  mass  becomes  still  denser  to 
form  the  anlage  of  the  skeletal  elements  of  the  extremity.  The  tissue  of  the 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


305 


core  shades  off  into  the  surrounding  tissue  of  a  lesser  density,  which  is  destined 
to  give  rise  to  the  muscles  and  which  is  known  as  the  premusde  sheath. 

During  these  processes  of  differentiation  in  the  limb  bud  proper,  masses  of 
premuscle  tissue  have  also  become  differentiated  around  the  base  of  the  limb 
bud.  These  are  the  forerunners  of  certain  extrinsic  muscles  of  the  upper  ex- 
tremity, such  as  the  pectoralis,  levator  scapula,  trapezius,  latissimus  dorsi,  ser- 
ratus,  etc.  (Fig.  273;  compare  with  Fig.  274). 


Spinal  ganglion 


Intervertebral  disk 

8th  cervical 
myotome 


Upper 
limb  bud 


Border  vein 


FlG.  271. — Transverse  section  through  the  8th  cervical  segment  of  a  human 
embryo  of  5  mm.     Lewis. 

By  the  end  of  the  fifth  week  the  premuscle  sheath  in  the  limb  bud  proper  be- 
comes more  or  less  differentiated  into  muscles  or  groups  of  muscles.  The 
differentiation  is  most  complete  at  the  proximal  end.  From  this  the  transition 
is  gradual  to  the  distal  end  where  the  premuscle  sheath  is  intact 

By  the  end  of  the  sixth  week  most  of  the  muscles  of  the  upper  extremity  are 
recognizable  (Figs.  274  and  275). 

By  the  end  of  the  seventh  week  practically  all  the  muscles  can  be  recognized 
and  are  composed  of  muscle  fibers. 

During  the  differentiation  of  the  muscles,  the  limb  bud  and  certain  ex- 
trinsic muscles  migrate  a  considerable  distance  caudally.  For  example,  the 


306 


TEXT-BOOK  OF  EMBRYOLOGY. 


pectoralis  and  latissimus  dorsi  migrate  from  the  base  of  the  arm  to  the  thoracic 
wall.  Their  nerves  are  naturally  pulled  with  them.  The  trapezius  muscle, 
which  originates  well  forward  in  the  cervical  region,  migrates  so  that  it  finally 
reaches  as  far  as  the  last  thoracic  vertebra.  The  sternomastoideus  also  origi- 
nates well  forward  in  the  cervical  region,  but  finally  extends  to  the  clavicle  and 
sternum.  The  migration  of  the  upper  extremity  causes  the  brachial  plexus  to 
have  a  caudal  inclination. 

The  lower  limb  buds  arise  very  soon  after  the  upper.     As  stated  on  page  153, 
the  upper  limbs  always  maintain  a  slight  advance  over  the  lower  in  develop- 


Spinal  ganglion 


Vertebral  arch 


8th  cerv.  myotome 

8th  cerv.  nerve 
6th,  7th  cerv.  nerv 
Condensed 
mesenchyme 


Border  vein 


Somatopleure 


FlG.  272. — Transverse  section  through  the  8th  cervical  segment  of  a  human 
embryo  of  7  mm.  (about  4  weeks).     Lewis. 


ment.  As  in  the  case  of  the  upper,  the  lower  limb  buds  appear  as  swellings  on 
the  ventro-lateral  surface  of  the  body,  opposite  the  fifth  lumbar  and  first  sacral 
myotomes.  The  interior  of  each  swelling  is  at  first  composed  of  closely  packed 
mesenchymal  tissue,  but  whether  any  part  of  the  myotomes  enters  it  is  question- 
able. At  all  events  several  spinal  nerves  do  enter  the  tissue  and  supply  the 
muscles.  The  differentiation  of  a  central  core  as  the  anlage  of  the  skeleton,  and 
the  differentiation  of  the  surrounding  tissue  as  the  premuscle  sheath,  take  place 
in  the  same  manner  as  in  the  upper  extremity  (p.  305) .  From  this  premuscle 
sheath  all  the  muscles  of  the  lower  extremity  are  developed. 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM.  307 

Histogenesis  of  Striated  Voluntary  Muscle  Tissue. 

The  majority  of  the  striated  voluntary  muscles  of  the  body  are  derived  from 
the  myotomes.  Some  are  derived  from  the  mesenchymal  tissue  in  the  branchial 
arches,  some  possibly  from  the  mesenchymal  tissue  in  the  limb  buds.  The 
primitive  segments  are  at  first  composed  of  closely  arranged,  epithelial-like  cells 
that  radiate  from  a  small  centrally  placed  cavity  (Fig.  141).  The  cavity  repre- 
sents part  of  the  ccelom  and  from  this  point  of  view  it  can  be  said  that  the  muscle 
is  a  derivative  of  the  epithelial  lining  of  the  coelom.  A  part  of  each  primitive 


Scapular 


Pectoral 


"Premuscle" 


Border  vein 


5th  nerve 

Phrenic  nerve 
Brachial  plexus 

Sympathetic 

Diaphragm 

Vertebra 


Hand  plate 


4th  rib 


FIG.  273. — Drawing  from  a  reconstruction  of  the  upper  limb  region  of  a  human 

embryo  of  9  mm.  (4^  weeks) ;  ventral  view.     Lewis. 

Inf.  hy.,  infrahyoid;  Lev.  scap.,  levator  scapulae;  My.,  myotome  mass;  Rhom., 
rhomboid;  Trap.,  trapezius. 

segment  becomes  the  sclerotome  and  cutis  plate.     The  remaining  part  be- 
comes the  myotome  or  muscle  plate  (Fig.  261). 

The  cells  of  the  myotome  are  at  first  not  essentially  different  from  those  of 
the  rest  of  the  primitive  segment.  Soon,  however,  changes  take  place  in  them 
and  they  become  the  so-called  myoblasts  or  muscle-forming  cells,  which  are 
destined  to  give  rise  to  the  muscle  fibers.  Opinions  differ  as  to  the  manner  in 
which  the  myoblasts  produce  the  muscle  fibers.  It  was  once  thought  that  each 
myoblast  gave  rise  to  a  single  muscle  fiber  in  which  there  were  several  nuclei,  all 


308  TEXT-BOOK  OF  EMBRYOLOGY. 

derived  from  the  original  myoblast  nucleus  by  mitotic  division.  It  was  also 
thought  that  the  muscle  fibrillae  represented  highly  modified  and  specialized 
parts  of  the  cytoplasm,  which  arranged  themselves  longitudinally  in  the  cell. 
Some  of  the  later  researches  indicate  that  a  muscle  fiber  represents  a  number  of 
myoblasts  fused  together.  This  explanation  is  not,  however,  accepted  by  all 
investigators. 

In  contrast  with  the  above,  there  is  a  quite  general  consensus  of  opinion  in 
regard  to  the  development  of  the  internal  structure  of  the  muscle  fiber.     In  the 


FIG.  274. — Lateral  view  of  a  reconstruction  of  the  muscles  of  the  upper  extremity  of  a  human 
embryo  of  16  mm.  (about  6  weeks).  Lewis. 

The  trapezius  is  the  large  muscle  arising  from  the  transverse  processes  of  the  vertebrae  (at  the  right 
of  the  figure)  and  converging  to  its  insertion  on  the  clavicle.  Just  below  the  insertion  of  the 
trapezius  is  the  deltoid,  which  partly  hides  the  subscapular  (on  the  right)  and  the  pectoralis 
major  (on  the  left).  Arising  beneath  the  deltoid  and  running  downward  to  the  elbow  is  the 
triceps.  To  the  right  of  the  triceps  is  the  teres  major  (composed  of  two  parts).  The  large 
sheet  of  muscle  extending  down  the  forearm  and  sending  divisions  to  the  2d,  30!,  4th  and  5th 
digits  is  the  extensor  communis  digitorum. 


cytoplasm  of  the  myoblasts  there  appear  granules  which  soon  arrange  them- 
selves in  parallel  rows  and  unite  to  form  slender  thread-like  fibrils  (Fig.  276). 
These  fibrils  are  at  first  confined  to  one  myoblast  area.  If  several  myoblasts 
fuse,  the  fibrils  probably  extend  in  a  short  time  from  one  myoblast  area  to 
another.  If  one  myoblast  produces  a  fiber,  the  fibrils  naturally  are  confined  to 
a  single  myoblast  area  throughout  development.  The  fibrils  are  usually 
formed  first  at  the  periphery  of  the  cell  and  later  in  the  interior  (Figs.  277 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM.  309 

and  278.)    At  the  same  time  they  increase  in  number  by  longitudinal  splitting. 
The  cytoplasm  among  the  fibrils  becomes  the  sarcoplasm. 

After  the  granules  which  first  appear  unite  to  form  the  fibrils,  the  latter 


FIG.  275. — Medial  view  of  a  reconstruction  of  the  muscles  of  the  upper  extremity  of  a  human 
embryo  of  16  mm.  (about  6  weeks).  Lewis. 

The  muscle  arising  on  the  scapula  (at  the  left  of  the  figure)  and  passing  toward  the  right  is  the 
subscapular.  The  small  muscle  just  below  the  subscapular  is  the  teres  major;  below  the 
latter  and  hanging  downward  is  the  latissimus  dorsi.  Note  the  cut  end  of  the  pectoralis 
minor  just  to  the  right  of  the  narrow  portion  of  the  subscapular.  Running  from  this  cut  end 
toward  the  right  is  the  biceps.  The  muscle  at  the  lower  edge  of  the  figure  in  the  arm  region 
is  the  triceps.  In  the  forearm  region,  the  muscle  crossing  the  end  of  the  biceps  is  the  pro- 
nator  teres.  Below  the  pronator  teres,  extending  from  the  elbow  to  the  thumb  region  is  the 
flexor  carpi  radialis.  Below  the  latter  and  extending  to  a  point  opposite  the  thumb,  is  the 
palmaris  longus.  Beneath  the  palmaris  longus  and  dividing  into  branches  which  pass  to  the 
sd,  3d,  4th,  and  5th  digits  is  the  flexor  sublimis  digitorum.  The  muscle  passing  to  the 
thumb  is  the  flexor  longus  pollicis.  The  muscle  at  the  lower  border  of  the  figure  in  the  fore- 
arm region  is  the  flexor  carpi  ulnaris. 


FIG.  276. — Myoblasts  in  different  stages  of  development.     Godlewski. 

The  upper  cell  represents  a  myoblast  with  granular  cytoplasm  (from  sheep  embryo  of  13  mm) ;  the 
middle,  a  myoblast  with  fibrils  in  process  of  formation  (from  guinea-pig  embryo  of  10  mm.); 
the  lower,  a  myoblast  with  still  further  differentiated,  segmented  fibrils  (from  a  rabbit 
embryo  of  8.5  mm.). 

are  apparently  quite  homogeneous.     Later  they  become  differentiated  into  two 
distinct  substances  which  alternate  throughout  their  length  and  produce  the 


310 


TEXT-BOOK  OF  EMBRYOLOGY. 


characteristic  cross  striation.  The  nature  of  this  differentiation  is  not  known. 
One  investigator  holds  that  both  substances  are  derived  from  the  original 
granules  that  unite  to  form  the  fibrils,  alternate  granules  being  composed  of  like 
substance  and  united  by  delicate  strands  of  the  other  substance. 

While  the  fibrils  are  being  formed,  the  nuclei  of  the  myoblasts  undergo  rapid 
mitotic  division.  When  the  cells  are  about  filled  with  fibrils,  the  nuclei  migrate 
to  the  periphery  where  they  are  situated  in  the  fully  formed  fiber  (Fig.  278). 
Each  fiber  thus  possesses  a  number  of  nuclei,  whether  it  is  derived  from  one 
myoblast  or  from  several. 


A.. 


x-T^rx        /  I  ^*V?)    7 

/£•$&&.  \\:Sy.^~^<,  //  fj  rU^//    •>  ^S>*/ 


FIG.  278 

FIG.  277. — From  a  cross  section  of  developing  voluntary  striated  muscle  in  the  leg  of  a  pig  embryo 

of  45  mm.,  showing  fibril  bundles  at  the  periphery  of  the  cells.     MacCallum. 
FIG.  278. — From  a  cross  section  of  developing  voluntary  striated  muscle  in  the  leg  of  a  pig  embryo 

of  75  mm.,  showing  fibril  bundles  more  numerous  than  in  Fig.  277.     A,  Central  vesicular 

nucleus;  B,  peripheral  more  compact  nucleus.     MacCallum. 


For  some  time  at  least,  the  number  of  fibers  in  a  developing  muscle  increases 
by  division  of  those  already  formed.  This  process  would  produce  a  certain 
degree  of  enlargement  of  the  muscle  as  a  whole.  Later  the  increase  in  the 
number  of  fibers  ceases,  and  the  muscle  grows  by  enlargement  of  the  individual 
fibers.  It  is  not  certain  at  what  period  in  development  the  increase  in  the  num- 
ber of  fibers  ceases. 

In  many  muscles  development  is  further  complicated  by  a  retrograde  proc- 
ess— a  degeneration  of  some  of  the  fibers.  This  occurs  quite  regularly  in  the 
extremities.  A  well  fibrillated  fiber  first  presents  a  homogeneous  appearance, 
then  becomes  vacuolated,  the  nuclei  disintegrate,  and  finally  the  whole 
structure  disappears.  Mesenchymal  (or  connective)  tissue  takes  its  place,  and 
the  remaining  fibers  are  thus  grouped  into  bundles  and  the  bundles  into 
muscles.  This  would  account  to  a  certain  extent  for  the  intermuscular  con- 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


311 


nective  tissue,  the  perimysium  and  endomysium,  the  epimysium  being  derived 
from  the  mesenchymal  tissue  which  originally  surrounded  the  muscle. 

THE  VISCERAL  MUSCULATURE. 

The  visceral  musculature  is  derived  wholly  from  the  mesoderm,  but  not 
from  the  myotomes.  The  striated  involuntary  muscle  or  heart  muscle  is  de- 
rived from  the  mesothelial  lining  of  the  coelom,  the  smooth  muscle  from  the 
mesenchymal  tissue  in  various  regions  of  the  body.  The  heart  muscle  develops 
only  in  connection  with  the  heart  and  consequently  occurs  in  the  adult  only  in 
that  organ.  Smooth  muscle  develops  to  form  integral  parts  of  certain  structures 
such,  for  example,  as  the  alimentary  tube,  glands,  blood  vessels,  and  skin. 

Histogenesis  of  Heart  Muscle. 

When  the  simple  tubular  heart  is  first  formed,  the  splanchnopleure  projects 
into  the  ccelom  (primitive  pericardial  cavity)  along  each  side  (Fig.  203;  also  p. 
227).  The  mesothelium  covering  these  projections  is  destined  to  give  rise  to 


FIG.  279. — From  a  section  of  developing  heart  muscle  from  a  rabbit  embryo  of  9  mm.     Godlewski. 

a,  Cell  body  with  granules  arranged  in  series;  b,  cell  body  with  centrosome  and  attraction  sphere; 

c,  branching  fibril;  d,  fibrils  extending  through  several  cells. 

the  myocardium.  The  mesothelial  cells  which  are  at  first  closely  packed  to- 
gether with  but  little  intercellular  substance,  assume  irregular  branching  forms 
and  the  branches  anastomose  freely  (Fig.  279).  After  the  cells  become  loosely 
arranged,  they  again  become  closely  packed  to  form  a  compact  syncytium,  in- 
dividual cells  apparently  assuming  the  shape  of  heavy  bands  (Fig.  280).  Ir- 
regular transverse  bands  next  appear,  dividing  the  syncytium  into  the  so-called 


312 


TEXT-BOOK  OF  EMBRYOLOGY. 


Heart  muscle  cells.  These  may  or  may  not  represent  the  original  cells  or 
myoblasts.  At  all  events  the  muscle  fibrils  are  continuous  across  the  lines. 
The  nuclei  proliferate  in  the  syncytium  but  remain  in  the  central  part  of  the 
bands  or  cells,  instead  of  migrating  to  the  periphery  as  in  striated  voluntary 
muscle. 

While  the  cells  are  still  loosely  arranged,  rows  of  granules  appear  in  the 
cytoplasm,  and  the  granules  in  each  row  unite  to  form  a  fibril  (Fig.  279) .     The 

fibrils  are  at  first  confined  to  individual 
cell  areas,  but  as  the  cells  come  closer 
together  to  form  the  compact  syncytium, 
they  extend  through  several  cell  areas 
and  run  in  different  directions  (Fig.  280) . 
As  development  proceeds  the  fibrils  be- 
come more  nearly  parallel  (Fig.  281). 
They  are  first  formed  in  the  peripheries 
of  the  cells,  but  later  also  in  the  interior, 
except  in  a  small  area  immediately  sur- 
rounding the  nucleus,  where  a  small 
amount  of  undifferentiated  cytoplasm 
remains.  The  latter  is  continuous 
with  the  cytoplasm  or  sarcoplasm 
among  the  fibrils.  As  in  voluntary 
striated  muscle  the  fibrils  become  differ- 
entiated into  two  distinct  substances 
which  alternate  with  each  other,  thus 
producing  the  transverse  striation. 


FlG.    280. — From   a   section   of    developing 
heart  muscle  in  a  rabbit  embryo  of  9  mm. 
Godlewski. 
The  cells  form  a  compact  syncytium. 


Histogenesis  of  Smooth  Muscle. 

The  mesenchymal  cells  which  are  destined  to  produce  smooth  muscle  cells 
are  not  grouped  into  any  particular  primitive  structures  like  the  mesodermic 
somites.  They  are  simply  scattered  through  the  general  mass  of  mesenchymal 
tissue  and,  like  other  mesenchymal  cells,  possess  irregular  branching  forms  and 
distinct  spherical  nuclei.  The  internal  changes  by  which  these  cells  are  con- 
verted into  muscle  cells  are  not  well  known.  The  contractile  elements — 
the  fibrillae — probably  represent  highly  modified  portions  of  the  original  cyto- 
plasm but  the  manner  in  which  the  cytoplasm  is  transformed  into  fibrillae  has 
not  been  determined.  The  external  changes  consist  essentially  in  an  elonga- 
tion of  the  irregular  mesenchymal  cells.  The  result  of  this  elongation  is  usually 
a  spindle-shaped  cell,  but  exceptionally  cells  forked  at  one  or  both  ends  are 
produced.  The  original  spherical  nucleus  also  shares  in  the  elongation  and 
becomes  rod-shaped. 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM. 


313 


In  some  cases,  for  example  in  the  muscular  layers  of  the  gastrointestinal 
tract,  distinct  bands  or  sheets  of  smooth  muscle  are  formed  in  which  the  cells 
are  closely  packed  and  lie  approximately  parallel.  In  other  cases,  such  as  the 
mucosa  of  the  intestine  and  the  capsules  of  certain  glands,  the  muscle  cells 
develop  in  little  groups  or  as  isolated  cells. 

Anomalies. 

More  or  less  of  the  muscular  system  is  involved  in  some  of  the  gross  anoma- 
lies or  malformations  of  the  body.  For  example,  congenital  defects  in  the  cen- 
tral nervous  system  (anencephaly,  rachichisis,  etc.)  are  necessarily  accompanied 
by  atrophy  or  faulty  development  of  certain  parts  of  the  muscular  system.  In 
the  case  of  ventral  median  fissure  of  the  abdominal  wall  (gastroschisis) ,  the 


FIG.  281. — From  a  section- of  developing  heart  muscle  in  a  rabbit  embryo  of  10  mm.     Godlewski. 
The  fibrils  are  segmented,  indicating  the  beginning  of  the  cross  striation  characteristic  of  heart  muscle. 

abdominal  muscles  are  naturally  involved.  Such  anomalies  in  the  muscles  are, 
however,  secondary  to  the  other  malformations  and  are  not  due  to  primary 
defects  in  the  muscles  themselves. 

Many  of  the  minor  variations  in  the  muscular  system  occur  in  the  same 
form  or  in  similar  forms  in  different  individuals,  thus  indicating  their  relation  to 
a  fundamental  type.  Many  of  these  are  more  or  less  accurate  repetitions  of 
normal  structures  found  in  lower  animals.  Such  variations  are  probably 
rightly  attributed  to  hereditary  influences.  On  the  other  hand,  there  are  varia- 
tions which  cannot  be  referred  to  conditions  found  in  any  of  the  lower  animals. 
These  constitute  a  class  of  variations  which  must  be  accounted  for  upon  some 
other  basis  than  that  of  heredity.  As  pointed  out  in  the  chapter  on  Teratogene- 
sis  (Chap.  XIX),  external  influences  undoubtedly  play  an  important  part  in  the 
production  of  anomalies  and  it  is  probable  that  similar  influences  act  upon  the 
development  of  the  muscular  system. 

The  scope  of  this  book  does  not  permit  a  description,  or  even  mention,  of  the 
great  number  of  variations  in  the  muscles.  A  few  are  described  here  as  ex- 


314  TEXT-BOOK  OF  EMBRYOLOGY. 

amples;  for  others  the  student  is  referred  to  the  more  extensive  text-books  of 
anatomy. 

EXTRINSIC  MUSCLES  OF  THE  UPPER  EXTREMITY. — The  trapezius  is  some- 
times attached  to  less  than  the  normal  number  of  thoracic  vertebrae.  Its 
occipital  attachment  may  be  wanting.  Occasionally  the  cervical  and  thoracic 
portions  are  more  or  less  separated  as  in  some  of  the  lower  animals. 

The  latissimus  dorsi  sometimes  arises  from  less  than  the  usual  number  of 
thoracic  vertebrae,  and  from  less  than  the  normal  number  of  ribs.  The  iliac 
origin  may  be  wanting. 

The  rhomboidei  vary  in  their  vertebral  and  scapular  attachments. 

The  number  of  the  vertebral  attachments  of  the  levator  scapulae  may  vary. 
A  small  part  of  the  muscle  is  sometimes  attached  to  the  occipital  bone. 

The  pectoralis  major  not  infrequently  varies  in  the  extent  of  its  attachment 
to  the  ribs  and  sternum. 

The  serrati  vary  in  their  attachment  to  the  ribs. 

The  above  mentioned  extrinsic  muscles  of  the  upper  extremity  vary  prin- 
cipally in  their  attachments.  Since  they  all  appear  well  forward  in  the  cervical 
region  in  the  embryo,  and,  along  with  the  extremity,  gradually  migrate  caudally 
before  acquiring  their  final  attachments,  it  is  not  unlikely  that  the  variations  in 
their  attachments  are  due  to  variations  in  the  extent  of  migration. 

This  serves  to  illustrate  a  factor  which  is  probably  important  in  producing 
variations  in  the  attachments  of  many  other  muscles.  As  stated  in  paragraph 
i,  on  page  295,  the  myotomes  frequently  migrate  very  extensively  during 
their  transformation  into  muscles,  before  the  muscles  have  acquired  their  per- 
manent attachment.  Variations  in  the  extent  of  this  migration  would  naturally 
produce  variations  in  the  final  attachments  of  these  muscles. 

Other  factors  related  to  the  changes  in  the  myotomes,  such  as  fusion,  longi- 
tudinal and  tangential  splitting  (paragraphs  2,  3  and  4,  p.  295)  probably  also 
play  a  part  in  the  production  of  variations. 

A  greater  than  normal  degree  of  fusion  between  two  or  more  myotomes 
might  result  in  the  union  of  muscles  which  are  usually  separate;  a  less  than 
normal  degree  of  fusion  might  result  in  the  separation  of  parts  usually  united. 
Variations  in  the  splitting  of  myotomes  might  produce  similar  results. 

At  the  same  time,  however,  heredity  may  be  the  active  factor  in  some  cases 
where  abnormal  fusions  or  separations  between  muscles  or  parts  of  muscles 
produce  results  resembling  conditions  found  in  lower  animals. 

Reference  for  Further  Study. 

BARDEEN,  C.  R.:  The  Development  of  the  Musculature  of  the  Body  Wall  in  the  Pig, 
Including  its  Histogenesis  and  its  Relation  to  the  Myotomes  and  to  the  Skeleton  and  to  the 
Nervous  Apparatus.  Johns  Hopkins  Hospital  Reports,  Vol.  XI. 


THE  DEVELOPMENT  OF  THE  MUSCULAR  SYSTEM.  315 

BARDEEX,  C.  R.,  and  LEWIS,  W.  H.:  Development  of  the  Limbs,  Body  Wall  and  Back 
in  Man.  American  Jour,  of  Anat.,  Vol.  I,  1901. 

BOLK,  L.:  Die  Segmentaldifferenzierung  des  menschlichen  Rumpfes  und  seiner  Extremi- 
taten.  Morph.  Jahrbuch,  Bd.  XXV,  1898. 

FUTAMURA,  R.:  Ueber  die  Entwickelung  der  Facialismuskulatur  des  Menschen. 
Anat.  Hefte,  XXX,  1906. 

GODLEWSKI,  E.:  Die  Entwickelung  des  Skelet-  und  Herzmuskelgewebes  der  Saugetiere. 
Arch.  }.  mik.  Anat.,  Bd.  LX,  1902. 

GRAFEXBERG,  E.:  Die  Entwickelung  der  menschlichen  Beckenmuskulatur.  Anat. 
Hefte,  1904. 

HEIDEXHAIX,  M.:  Structur  der  contractilen  Materie.  Ergebnisse  der  Anat.  u.  Entivick., 
Bd.  VIII,  1898. 

HEIDEXHAIX,  M.:  Ueber  die  Structur  des  menschlichen  Herzmuskels.  Anat.  Anz., 
Bd.  XX,  1901. 

KASTXER,  S.:  Ueber  die  Bildung  von  animalen  Muskelfasern  aus  dem  Urwirbel. 
Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  Suppl.,  1890. 

KEIBEL,  F.,  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  Vol.  I,  1910. 

KOLLMAXX,  J.:  Die  Rumpfsegmente  menschlicher  Embryonen  von  13-35  Urwirbeln. 
Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1891. 

LEWIS,  W.  H.:  The  Development  of  the  Arm  in  Man.  American  Jour,  of  Anat.,  Vol.  I, 
1902. 

MAURER,  F.:  Die  Entwickelung  des  Muskelsystems  und  der  elektrischen  Organe.  Also 
Bibliography.  In  Hertwig's  Handbuch  der  vergl.  u.  experiment.  Entwickelungslehre  der 
Wirbeltiere,  Bd.  Ill,  Teil  I,  1904. 

MACCALLUM,  J.  B.:  On  the  Histology  and  Histogenesis  of  the  Heart -muscle  Cell. 
Anat.  Anz.,  Bd.  XIII,  1897. 

MACCALLUM,  J.  B.:  On  the  Histogenesis  of  the  Striated  Muscle  Fiber  and  the  Growth  of 
the  Human  Sartorius  Muscle.  Johns  Hopkins  Hospital  Bulletin,  Vol.  IX,  1898. 

MALL,  F.  P.:  Development  of  the  Ventral  Abdominal  Walls  in  Man.  Jour,  of  Mor- 
phology, Vol.  XIV,  1898. 

McGiLL,  CAROLIXE:  The  Histogenesis  of  Smooth  Muscle  in  the  Alimentary  Canal  and 
Respiratory  Tract  of  the  Pig.  Internal.  Monatsch.  Anat.  u.  Phys.,  Bd.  XXIV,  1907. 

McMuRRicH,  J.  P.:  The  Phylogeny  of  the  Forearm  Flexors.  American  Jour,  of  Anat., 
Vol.  II,  1903. 

McMuRRicH,  J.  P.:  The  Phylogeny  of  the  Palmar  Musculature.  American  Jour,  of 
Anat.,  Vol.  II,  1903. 

MCMURRICH,  J.  P.:  The  Phylogeny  of  the  Crural  Flexors.     American  Jour,  cf  Ana!., 

Vol.  rv,  1904. 

MCMURRICH,  J.  P.:  The  Phylogeny  of  the  Plantar  Musculature.  American  Jour,  of 
Anat.,  Vol.  VI,  1907. 

POPOWSKY,  L:  Zur  Entwickelungsgeschichte  der  Dammmuskulatur  beim  Menschen. 
Anat.  Hefte,  1899. 

SUTTOX,  J.  B.:  Ligaments,  Their  Nature  and  Morphology.     London,  1897. 

ZIM.MERILA.XX:  Ueber  die  Metamerie  des  Wirbeltierkopfes.  Verhandl.  d.  Anat.  Gesellsch. 
Jena,  1891. 


CHAPTER  XII. 

THE  DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND 
APPENDED  ORGANS. 

The  embryonic  disk,  composed  of  the  three  germ  layers,  primarily  lies  flat 
upon  the  yolk  sac  (see  p.  135;  also  Fig.  82).  A  little  later  the  axial  portion  of 
the  embryo  is  indicated  by  the  primitive  streak,  the  neural  groove  (subsequently 
the  neural  tube),  the  notochord,  and  the  primitive  segments  (Fig.  74).  Then 
along  each  side  of  the  axial  portion  and  at  the  cephalic  and  caudal  ends,  the 


Allantoic  duct 


Belly  stalk 


FIG.  282. — Lateral  view  of  human  embryo  with  14  pairs  of  primitive  segments  (2.5  mm.) .     Kollmann. 

The  yolk  sac  has  been  cut  off.     The  fore-gut,  mid-gut  and  hind-gut,  as  indicated  in  the  figure, 

together  constitute  the  primitive  gut.     Compare  with  Fig.  283. 

germ  layers  bend  ventrally  and  medially  and  finally  meet  and  fuse  in  the  mid- 
ventral  line  (p.  137).  The  portion  of  the  entoderm  ventral  to  the  notochord  is 
bent  into  a  tube  which,  for  the  most  part,  becomes  pinched  off  from  the  parent 
entoderm  and  is  suspended  in  the  embryonic  coelom  by  the  common  mesentery 
(Figs.  141  and  142).  This  entodermal  tube  is  the  primitive  gut.  At  first  it  is 
but  slightly  elongated  and  is  closed  at  both  ends.  On  the  ventral  side,  however; 

316 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       317 

it  opens  widely  into  the  yolk  sac  (Figs.  282  and  283).  The  primitive  gut,  there- 
fore, has  no  communication  with  the  exterior.  It  communicates  at  its  caudal 
end  with  the  central  canal  of  the  spinal  cord  through  the  neurenteric  canal  (Fig.  84; 
compare  with  85). 

As  development  proceeds,  this  simple  tube  elongates  rapidly  and  becomes 
differentiated  into  distinct  regions.  The  cephalic  end,  in  connection  with  the 
branchial  arches  and  grooves,  becomes  the  dilated  pharyngeal  region.  Caudal 


Oral  fossa 
Branchial  arch  I 
Branchial  arch  II 

Body  wall 
Coelom 

Fore-gut 
Mid-gut 

Ccelom 
Hind-gut 

Belly  stalk 


FIG.  283. — Ventral  view  of  human  embryo  of  2.4  mm.     His,  Kollmann. 

Note  the  opening  in  the  ventral  wall  of  the  gut.     This  indicates  the  communication  between  the 
gut  and  the  yolk  sac.     The  latter  has  been  removed.     Compare  with  Fig.  282. 

to  and  continuous  with  this,  is  the  short,  narrow  ossophageal  region  which  in 
turn  passes  over  into  the  slightly  dilated  stomach  region.  The  portion  of  the 
gut  caudal  to  the  stomach  is  the  intestinal  region.  During  the  differential 
changes,  the  communication  with  the  yolk  sac  becomes  relatively  smaller,  form- 
ing the  yolk  stalk  which  joins  the  intestinal  portion  a  short  distance  caudal  to  the 
stomach  (Figs.  284  and  285). 

The  Mouth. 

At  a  very  early  period  the  primary  fore-brain  region  bends  ventrally  almost 
at  a  right  angle  to  the  long  axis  of  the  body  to  form  the  naso-frontal  process. 


318 


TEXT-BOOK  OF  EMBRYOLOGY. 


As  the  first  branchial  arch  develops,  it  grows  ventrally  until  it  meets  and  fuses 
with  its  fellow  of  the  opposite  side  in  the  midventral  line,  thus  forming  the 
mandibular  process.  From  the  cephalic  side  of  the  first  arch  a  secondary  proc- 
ess— maxillary  process — develops  and  fills  in  the  space  between  the  arch  itself 
and  the  naso-frontal  process.  These  various  structures  thus  bound  a  distinct 
depression  on  the  ventral  side  of  the  head.  This  depression  is  the  oral  pit,  the 
forerunner  of  the  oral  and  nasal  cavities  (Fig.  283;  compare  with  Figs.  282 
and  122) .  The  groove  in  the  midventral  line  between  the  mandibular  processes 
marks  the  symphysis  of  the  lower  jaws.  The  groove  on  each  side  between  the 


Epiglottis 

Tongue 
Hypophysis 


Larynx 


Lung 


g.  L..\ —  Stomach 


A—--   Pancreas 


Urachus 


Mesonephric  duct 


Kidney  bud 


FIG.  284 — Alimentary  tube  of  a  human  embryo  of  4.1  mm.     His  Kollmann. 


maxillary  process  and  the  mandibular  process  marks  the  angle  of  the  mouth, 
The  groove  between  the  maxillary  process  and  the  naso-frontal  process  is  the 
naso-optic  furrow,  at  the  dorsal  end  of  which  the  eye  develops. 

The  bottom  of  the  oral  pit  is  formed  by  a  portion  of  the  ventral  body  wall, 
which  separates  the  oral  cavity  from  the  cephalic  end  of  the  gut,  and  which  is 
composed  of  ectoderm  and  entoderm,  with  a  small  amount  of  mesoderm  be- 
tween. This  closing  plate,  the  pharyngeal  membrane,  which  is  still  present  in 
embryos  of  2.15  mm.,  soon  becomes  thinner  and  finally  breaks  away,  leaving 
the  oral  pit  and  the  gut  in  direct  communication  (Fig.  285).  Since  the  oral  pit 
is  lined  with  ectoderm,  the  epithelial  lining  of  the  mouth  or  oral  cavity  is  largely  of 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       319 


ectodermal  origin.  In  the  medial  line  of  the  roof  of  the  ofal  cavity,  near  the 
pharyngeal  membrane,  the  epithelium  (ectoderm)  evaginates  to  form  Rathke's 
pocket.  This  comes  in  contact  with  an  evagination  from  the  floor  of  the  brain 
and  with  it  forms  the  pituitary  body. 

The  further  development  of  the  mouth  consists  of  an  elaboration  of  the 
structures  which  primarily  bound  the  oral  pit  and  the  growth  of  certain  new 
structures  such  as  the  teeth  and  the  tongue.  The  first  branchial  arch  fuses  with 
its  fellow  of  the  opposite  side  in  the  midventral  line  to  form  the  symphysis  of 
the  lower  jaws,  giving  rise  also  to  the  lower  lip  and  chin  region.  As  the  naso- 
frontal  process  continues  to  grow,  two  depressions  appear  on  its  ventral  border, 


Pharynx 


Hypophysis 

Yolk  sac 

Belly  stalk 
Caudal  gut 


Branchial  arches 
(pharynx) 


Lung 

Liver 

Stomach 

Pancreas 

Common 
mesentery 

Mesonephros 
Allantoic  duct 

Hind-gut 


Kidney  bud 
FIG.  285. — Sagittal  section  of  reconstruction  of  a  human  embryo  of  5  mm.     His,  Kollmann. 

one  on  each  side,  a  short  distance  from  the  medial  line.  These  depressions  are 
the  nasal  pits  which  indicate  the  beginning  of  the  external  openings  of  the  nasal 
passages.  The  part  between  the  nasal  pits  is  destined  to  give  rise  to  the  nasal 
septum  and  the  medial  part  of  the  upper  lip  (Fig.  136).  The  primary  oral 
cavity  is  divided  into  the  oral  cavity  proper  and  the  nasal  cavity  by  outgrowths 
from  the  maxillary  processes.  From  the  medial  side  of  each  maxillary  process 
a  plate-like  structure  grows  across  the  primary  oral  cavity  toward  the  medial 
line  (Fig.  178).  These  two  plates,  or  palatine  processes,  meet  and  fuse  with  the 
lower  part  of  the  nasal  septum  (Fig.  286) .  (For  further  details  of  this  fusion,  see 
page  148  and  page  195).  The  palatine  processes  thus  form  the  palate,  or  the 
roof  of  the  mouth,  which  separates  the  mouth  cavity  from  the  nasal  cavity.  The 
palate  does  not  extend  far  enough  backward,  however,  to  separate  the  posterior 


320 


TEXT-BOOK  OF  EMBRYOLOGY. 


part  of  the  nasal  cavity  from  the  pharynx.  Thus  the  posterior  nares  and 
pharynx  are  left  in  communication.  Externally  the  maxillary  processes  extend 
medially,  separate  the  nasal  pits  from  the  oral  cavity,  and  form  the  lateral 
portions  of  the  upper  lip  (Fig.  137). 


Jacobson's  organ 
Inferior  concha 

Jacobson's  cartilage 


Palatine  process 


Nasal  septum 


Nasal  cavity 


Oral  cavity 


FIG.  286. — From  a  section  through  the  head  of  a  human  embryo  of  28  mm.,  showing  the  nasal 
septum,  the  nasal  cavities,  the  oral  cavity,  and  the  palatine  processes.     Peter. 

The  Tongue. — The  tongue  develops  from  three  separate  anlagen  which 
unite  secondarily.  In  embryos  of  about  3  mm.  a  slight  elevation  appears  on  the 
floor  of  the  pharynx  in  the  region  of  the  first  branchial  arch.  This  is  the 


Tuberculum  impar 


Root  of  tongue 


Inner  branchial 
groove  IV 


Crista  terminalis 


Lung 
FIG.  287. — Floor  of  the  pharyngeal  region  of  a  human  embryo  of  about  3  weeks.     His. 

tuberculum  impar,  being,  as  the  name  indicates,  unpaired,  and  is  destined  to  give 
rise  to  the  tip  and  body  of  the  tongue  (Fig.  287) .  Soon  afterward  two  bilaterally 
symmetrical  elevations  appear  on  the  floor  of  the  pharynx,  which  are  destined  to 
give  rise  to  the  root  of  the  tongue  (Fig.  288).  These  paired  elevations,  arising 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       321 

in  the  region  of  the  second  and  third  branchial  arches,  gradually  enlarge  and 
unite  with  each  other  and  with  the  tuberculum  impar,  leaving  between  the 
latter  and  themselves,  however,  a  V-shaped  groove  (Fig.  289).  At  the  apex  of 
the  groove  there  is  a  depression — the  foramen  ccecum  lingua — which  is  the  ex- 
ternal opening  of  the  thyreoglossal  duct  (see  p.  332).  The  groove  later  disap- 
pears, but  its  position  is  indicated  in  the  adult  by  the  vallate  papillae. 

According  to  Hammar,  the  tuberculum  impar  is  a  transitory  structure  and  does  not 
give  rise  to  the  tip  and  body  of  the  tongue.  The  tip  and  body  are  derived  from  a  much 
more  extensive  elevation  in  the  floor  of  the  pharynx. 

The  tongue  as  a  whole  enlarges  and  grows  from  its  place  of  origin  toward 
the  entrance  to  the  primary  oral  cavity.  For  a  time  it  practically  fills  the  cavity. 
When  the  palate  develops  it  recedes  and  finally  comes  to  lie  on  the  floor  of  the 
oral  cavity  proper,  as  in  the  adult.  The  growth  of  the  tongue  involves  the 


Tuberculum  impar 

Root  of  tongue 
Epiglottis 

FIG.  288. — Floor  of  pharyngeal  region  of  a  human  embryo  of  12.5  mm.     His. 

epithelial  lining  of  the  pharynx  and  oral  cavity  and  also  the  underlying  mesen- 
chymal tissue.  The  latter  produces  the  connective  tissue  and  at  least  a  part  of 
the  intrinsic  muscle  fibers  of  the  tongue.  The  papillae  involve  the  epithelium 
and  connective  tissue,  while  the  glands  and  taste  buds  are  derived  from  the 
epithelium  alone. 

The  portion  of  the  lingualis  muscle  innervated  by  the  facial  (VII)  nerve  is  probably 
derived  from  the  mesenchymal  tissue  in  the  tongue  anlage.  The  rest  of  the  muscle  is 
innervated  by  fibers  from  the  hypoglossal  (XII)  nerve,  indicating  a  possible  derivation  from 
certain  rudimentary  segments  in  the  occipital  region  which  correspond  to  the  three  roots  of 
the  nerve.  This  would  make  it  appear  that  during  phylogenesis  a  part  of  the  lingualis 
muscle  has  grown  into  the  tongue  from  a  region  caudal  to  the  last  branchial  arch 

The  lingual  papilla  begin  to  develop  during  the  third  month.  Their 
development  is  limited  to  the  dorsum  of  the  tongue  and  to  the  portion  derived 
from  the  tuberculum  impar.  In  other  regions  slight  elevations  may  appear,  but 
not  in  the  form  of  distinct  papillae.  The  jungijorm  and  filijorm  papillae  appear 
as  pointed  elevations  in  the  connective  tissue,  which  push  their  way  into  the 
epithelium,  the  latter  at  the  same  time  being  raised  above  the  surface  over  these 


322  TEXT-BOOK  OF  EMBRYOLOGY. 

points.  Gradually  the  little  masses  of  connective  tissue  assume  the  shapes 
characteristic  of  fungiform  or  filiform  papillae.  During  the  fifth  month 
the  epithelium  between  the  papillae  apparently  degenerates  to  some  extent, 
thus  leaving  them  projecting  still  farther  above  the  surface.  The  forma- 
tion of  papillae  probably  goes  on  for  some  time  after  birth,  since  at  birth  their 
form,  size,  number  and  arrangement  are  not  the  same  as  at  later  periods.  It  is 
an  interesting  fact  that  the  filiform  papillae  lose  many  of  their  taste  buds  after 
the  child  is  weaned. 

The  anlage  of  the  vallate  papillae  appears  as  a  ridge  along  the  V-shaped  line 
of  fusion  between  the  paired  and  unpaired  portions  of  the  tongue.  The  ridge  is 
apparently  formed  by  the  ingrowth  of  a  solid  mass  of  epithelium  along  each 
side,  although  the  connective  tissue  between  the  masses  may  grow  toward  the 
surface  to  some  extent.  Later  the  ridge  is  broken  up  into  the  individual  papillae 

Tuberculum  impar 

Root  of  tongue 


Epiglottis 
'  Larynx 
FIG.  289. — Dorsal  view  of  the  tongue  of  a  human  embryo  of  20  mm.     His,  Bonnet. 

by  the  ingrowth  of  the  epithelium  at  certain  points.  The  more  superficial  cells 
of  the  masses  then  degenerate,  thus  leaving  each  papilla  surrounded  by  a  trench 
and  wall. 

The  development  of  the  lingual  glands  is  confined  for  the  most  part  to  the 
root  and  inferior  surface  and  to  the  region  of  the  vallate  papillae.  The  glands 
begin  to  develop  during  the  fourth  month  as  solid  ingrowths  of  epithelium,  the 
mucous  glands  appearing  first,  the  serous  somewhat  later.  The  epithelial 
masses  acquire  lumina  and  grow  deeper  into  the  tongue,  where  they  usually 
branch  and  coil  to  form  the  secreting  portions.  The  latter  open  to  the  surface 
through  the  original  ingrowths  which  become  the  ducts.  Ebner's  glands 
develop  from  the  bottoms  of  the  trenches  around  the  vallate  papillae. 

The  Teeth. — The  development  of  the  teeth  involves  the  ectoderm  and 
mesoderm,  the  former  giving  rise  to  the  enamel,  the  latter  to  the  dentine  and 
pulp.  In  human  embryos  of  12-15  mm-  (thirty-four  to  forty  days),  before 
the  lip  groove  is  formed,  a  thickening  of  the  epithelium  (ectoderm)  takes  place 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       323 

along  the  edges  of  the  processes  that  bound  the  slit-like  entrance  to  the  mouth. 
When  the  lip  groove  appears  (Fig.  178),  the  epithelial  thickening  comes  to  lie 
along  the  edge  of  the  jaw,  or  in  other  words,  along  the  edge  of  the  gums.  It 
then  grows  into  the  mesenchymal  tissue  (mesoderm)  of  the  jaw  obliquely  toward 
the  lingual  surface  to  form  the  dental  shelf.  A  little  later  the  dental  groove 
appears  on  the  edge  of  the  jaw,  along  the  line  where  the  ingrowth  of  epithelium 
took  place. 


Epithelium  of  mouth  cavity 


Inner 
enamel  cells 


Dental  papilla    -J-H 


Neck  of 
enamel  organ 


Germ  of 
permanent  tooth 


M  Bone  of 
lower  jaw 


FIG.  290. — Section  of  developing  tooth  from  a  3^  months  human  foetus.     Szymonowicz. 

Note  the  portion  of  the  original  dental  shelf  connecting  the  developing  tooth  with  the 

epithelium  of  the  mouth  cavity. 


The  dental  shelf  is  at  first  of  uniform  thickness,  but  in  a  short  time  five 
enlargements  appear  in  it  in  each  upper  and  lower  jaw,  indicating  the  begin- 
nings of  the  milk  teeth.  When  the  embryo  reaches  a  length  of  40  mm.  (an  age  of 
eleven  to  twelve  weeks)  the  mesenchymal  tissue  on  one  side  of  these  enlargements 
(above  and  to  the  inner  side  in  the  upper  jaw,  below  and  to  the  inner  side  in  the 
lower  jaw)  becomes  condensed  and  pushes  its  way  into  the  epithelium.  Each  of 
these  mesenchymal  ingrowths  is  a  dental  papilla.  Thus  at  this  stage  the  anlage 
of  each  tooth  is  a  mass  of  epithelium  fitting  cap-like  over  a  mesenchymal  papilla. 
The  epithelium  is  the  forerunner  of  the  enamel  organ;  the  papilla  is  destined  to 
give  rise  to  the  dentine  and  pulp.  The  anlagen  are  connected  with  one  another 


324 


TEXT-BOOK  OF  EMBRYOLOGY. 


by  intermediate  portions  of   the  dental  shelf,  and  with  the  surface  by  the 
original  ingrowth  of  epithelium. 

THE  ENAMEL. — The  epithelial  cells  nearest  the  dental  papilla  become  high 
columnar  in  shape,  forming  a  single  layer.  Those  in  the  interior  of  the  mass 
become  separated  and  changed  into  irregular,  stellate,  anastomosing  cells,  with 
a  fluid  intercellular  substance,  constituting  the  enamel  pulp.  Those  farthest 
from  the  papilla  become  flattened  (Fig.  290;  compare  with  Fig.  291).  Calcifi- 
cation begins  in  the  basal  ends  of  the  columnar  cells,  or  in  the  ends  next  the 


Enamel 
Dentine         j     Enamel  prisms 


Odontoblasts 


r. 

*-a~         --rr-    Outer } 

I  enamel 
_  cells 

-    Inner  J 


Enamel  pulp 


FIG.  291. — Section  through  the  border  of  a  developing  tooth  of  a  new-born  puppy.     "Bonnet. 

papilla,  and  in  the  intercellular  substance,  and  gradually  progresses  throughout 
the  cells,  the  latter  at  the  same  time  becoming  much  more  elongated.  Thus  the 
cells  are  transformed  into  enamel  prisms  which  are  held  together  by  the  calci- 
fied intercellular  substance  (Fig.  291). 

The  formation  of  enamel  begins  in  the  milk  teeth  toward  the  end  of  the 
fourth  month  and  probably  continues  until  the  teeth  break  through  the  gums. 
The  enamel  organ  at  first  surrounds  the  entire  developing  tooth  except  where 
the  papilla  joins  the  underlying  mesenchymal  tissue  (Fig.  290).  Later  the 
deeper  part  of  the  organ  disappears  as  such,  and  the  enamel  is  formed  only  on 
that  part  of  the  tooth  which  eventually  becomes  the  crown.  The  enamel  pulp 
increases  in  amount  for  a  time,  but  subsequently  disappears  as  the  tooth  grows 
into  it  (Fig.  292).  Its  function  is  not  fully  understood.  It  may  serve  as  a  line 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       325 

of  least  resistance  in  which  the  tooth  grows,  and  it  may  convey  nourishment 
to  the  enamel  cells,  the  enamel  organ  being  non-vascular. 

The  Dentine  and  Pulp. — At  first  the  dental  papilla  is  simply  a  condensation 
of  mesenchyme,  but  later  it  is  converted  into  a  sort  of  connective  tissue  pene- 
trated by  blood  vessels  and  nerves  (Fig.  292).  The  cells  nearest  the  enamel 
organ  become  columnar  and  arranged  in  a  single  layer,  with  the  nuclei 
toward  their  inner  ends.  The  outer  ends  are  blunt,  while  the  inner  ends  are 


Epith.  of  mouth  cavity 


Outer) 

>  enamel  cells 


Dental  sac 


Bone  of  jaw 


Blood  vessel 


Enamel  pulp 
(remnant) 


Papilla 
FIG.  292. — Longitudinal  section  of  a  developing  tooth  of  a  new-born  puppy.     Bonnet. 

continued  as  slender  processes  that  extend  into  the  pulp  and  probably  fuse 
with  other  cell  processes.  These  columnar  cells  are  the  odontoblasts,  under  the 
influence  of  which  the  lime  salts  of  the  dentine  are  deposited,  and  which  are  com- 
parable with  the  osteoblasts  in  developing  bone. 

Toward  the  end  of  the  fourth  month  the  odontoblasts  form  a  membrane- 
like  structure,  the  membrana  preformativa,  between  themselves  and  the  enamel. 
This  membrane  is  first  converted  into  dentine  by  the  deposition  of  lime  salts, 
after  which  the  process  of  calcification  progresses  from  the  enamel  toward  the 


326  TEXT-BOOK  OF  EMBRYOLOGY. 

pulp.  During  calcification  slender  processes  of  the  odontoblasts  remain  in  minute 
channels,  or  dentinal  canals,  forming  the  dentinal  fibers  which  anastomose  with 
one  another  (Fig.  291).  In  the  peripheral  part  of  the  dentine  certain  areas 
apparently  fail  to  become  calcified  and  form  the  inter  globular  spaces.  The  same 
cells  that  are  originally  differentiated  from  the  mesenchyme  probably  persist 
throughout  development  as  the  odontoblasts  and  produce  the  entire  amount  of 
dentine  in  a  tooth.  Even  in  the  fully  formed  tooth  there  is  a  layer  of  odonto- 
blasts bearing  the  same  relation  to  the  dentine  and  pulp  as  in  the  developing 
tooth.  The  chief  difference  between  dentine  formation  and  bone  formation  is 
that  in  the  latter  the  osteoblasts  become  enclosed  to  form  bone  cells,  while  in 
the  former  the  odontoblasts  merely  leave  processes  enclosed  as  the  cell  bodies 
recede. 

The  pulp  of  the  tooth  is  of  course  derived  from  the  mesenchymal  tissue  in 
the  interior  of  the  dental  papilla  (compare  Figs.  290  and  292).  The  blood 
vessels  and  nerves  grow  in  from  the  underlying  connective  (mesenchymal)  tissue. 

At  an  early  stage  the  mesenchymal  tissue  around  the  anlage  of  the  tooth,  in- 
cluding the  enamel  organ,  condenses  to  form  a  sort  of  sheath,  the  dental  sac, 
which  is  later  ruptured  when  the  tooth  breaks  through  the  gum  (Fig.  292). 
The  cement  is  formed  around  the  root  of  the  tooth  from  the  tissue  of  the  dental 
sac  in  the  same  manner  as  subperiosteal  bone  is  formed  from  osteogenetic  tissue 
(p.  174).  In  fact,  cement  is  true  bone  without  Haversian  systems. 

The  milk  teeth,  which  are  the  first  to  develop  and  the  first  to  appear  above 
the  surface,  are  represented  by  the  medial  incisors,  lateral  incisors,  canines,  and 
molars,  to  the  number  of  ten  in  the  upper  and  ten  in  the  lower  jaw.  They  may 
be  indicated  graphically  thus: 


M. 

C. 

L.I. 

M.I. 

M.I. 

L.I. 

C. 

M. 

2 

i 

i 

i 

i 

i 

i 

2 

2 

i 

i 

i 

i 

i 

i 

2 

M. 

C. 

L.I. 

M.I. 

M.I. 

L.I. 

C. 

M. 

-^-=20 
IO 


In  describing  the  formation  of  the  dental  shelf,  it  was  noted  that  the  papilke 
of  the  milk  teeth  grow  into  corresponding  thickenings  of  the  epithelium  (p.  323). 
The  growth  takes  place  from  the  side,  thus  leaving  the  edge  of  the  shelf  free  to 
grow  farther  toward  the  lingual  side  of  the  jaw.  In  this  free  edge  other  tooth 
germs  arise,  which  mark  the  beginnings  of  the  permanent  teeth  (Fig.  290).  In 
addition  to  the  germs  that  correspond  in  position  to  the  milk  teeth,  three  others 
arise  in  each  jaw,  representing  the  true  molars  of  the  adult.  The  latter  arise  in  a 
part  of  the  dental  shelf  which  has  grown  toward  the  articulation  of  the  jaws 
without  coming  in  contact  with  the  surface  epithelium.  The  first  papilla  of 
the  permanent  dentition  to  appear  is  that  of  the  first  molar.  It  appears  im- 
mediately behind  the  second  milk  molar  at  a  time  when  the  milk  teeth  are  well 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       327 


advanced  (embryos  of  180  mm.,  about  seventeen  weeks).  The  permanent 
incisors  and  canines  appear  about  the  twenty-fourth  week;  the  premolars,  which 
correspond  to  the  milk  molars,  about  the  twenty-ninth  week.  The  second 
molar  does  not  appear  till  after  birth  (six  months),  and  the  third  molar,  or 
wisdom  tooth,  begins  to  develop  about  the  fifth  year. 

The  formation  of  the  anlagen  of  the  permanent  teeth  and  the  development  of 
the  enamel,  dentine  and  pulp  take  place  in  precisely  the  same  manner  as  in  the 
milk  teeth.  The  true  molars  grow  out  through  the  gums  in  the  same  way  as 
the  milk  teeth.  Those  permanent  teeth  which  correspond  in  position  to  milk 
teeth  grow  under  the  latter,  exert  pressure  on  their  roots  and  thus  loosen  and 
finally  replace  them.  The  two  sets  of  teeth  may  be  graphically  represented 
thus: 


16 


Normally  all  the  epithelium  of  the  dental  shelf,  except  the  parts  directly  con- 
cerned in  the  development  of  the  teeth,  disappears  at  times  which  vary  in  differ- 
ent individuals.  Occasionally,  however,  remnants  of  this  epithelium  give  rise 
to  cystic  structures  (developmental  tooth  tumors). 


:^':-_-  Tongue 
•P. 


Upper 
Upper 

Jaw  —  Permanent, 

Taw—  Milk, 

M. 

Pm. 

II 
M 

C. 

II 

c 

L.I. 

II 
L  T 

M.I. 

A 

M.I. 

M"T 

L.I. 

T"T 

c. 

II 
c 

Pm. 

,!! 

M. 

1! 

3 

2 

I 

2 

1 

Lower 
Lower 

Jaw—  Milk, 
Taw  —  Permanent, 

3 
M. 

2 

M. 

I 

I 

c. 

! 

i 
L.I. 

T!'T 

I 
M.I. 

Jl 

M.I. 

J'i 

I 

L.I. 

A 

I 

c. 

II 

c. 

2 
M. 

Pi 

3 

I 

Subling.  gland 


Submax.  gland 


Palatine  process 


Submax.  gland 


Lingual  nerve 
FIG.  293. — From  a  transverse  section  through  the  tongue  and  oral  cavity  of  a  mouse  embryo.    Goppert, 

The  Salivary  Glands. — The  anlage  of  the  submaxillary  gland  appears,  in 
embryos  of  10  to  12  mm.,  as  a  flange  of  epithelium  directed  ventrally  from 
the  portion  of  the  lingual  sulcus  just  caudal  to  the  crossing  of  the  lingual 
nerve.  The  flange  grows  into  the  mesenchyme  of  the  lower  jaw,  and  at  an 
early  period  becomes  triangular  with  its  longest  side  free  and  a  free  vertical 
caudal  border.  Cell  proliferation  begins  at  the  angle  of  union  of  the  two 
borders  and  gradually  progresses  cephalad  along  the  longest  border,  thus 
producing  a  solid  ridge-like  thickening  of  the  latter. 


328  TEXT-BOOK  OF  EMBRYOLOGY. 

The  main  portion  of  the  gland  is  produced  by  a  sprouting  of  the  epithelium 
from  the  angle  of  union  of  the  two  free  borders  of  the  flange  and  grows  deep 
into  the  mesenchyme  along  the  mesial  side  of  the  ramus  of  the  mandible. 
The  sprouts  branch  repeatedly  in  the  course  of  their  development,  thus  laying 
the  foundation  for  the  division  of  the  gland  into  lobes  and  lobules. 

The  distal  end  of  the  duct  of  the  submaxillary  (Wharton's)  is  formed  from 
the  ridge-like  thickening  of  the  free  margin  of  the  flange  through  a  dissolu- 
tion of  the  greater  part  of  the  flange  between  the  lingual  sulcus  and  the 
thickened  margin  itself,  thus  freeing  this  portion  of  the  duct  from  the  sulcus. 
By  a  continuation  of  the  growth  which  produced  the  ridge  along  the  free 
border  of  the  original  flange  an  extension  of  this  same  ridge  is  produced  along 
the  bottom  of  the  lingual  sulcus  forward  toward  the  chin  region.  This  portion 
of  the  ridge  is  progressively  constricted  off  from  the  sulcus  from  behind 
forward,  until  finally  the  attachment  of  the  duct  reaches  its  definitive  position 
at  the  side  of  the  frenulum  linguae. 

The  anlage  of  the  Bartolinian  element  of  the  sublingual  gland  appears  as 
a  smaller  flange  attached  to  the  lateral  border  of  the  submaxillary  flange  near 
the  crossing  of  the  lingual  nerve  and  prolonged  forward  by  an  interrupted 
crest  along  the  lingual  sulcus.  Its  later  development  is  similar  to  that  of  the 
submaxillary. 

A  small  medial  flange  also  on  the  submaxillary  flange  gives  rise  to  a  sprout 
in  much  the  same  manner  as  the  other  anlagen.  While  the  history  of  this 
anlage  is  not  complete  in  the  human  embryo,  it  probably  gives  rise  to  the 
anterior  lingual  gland  (gland  of  Blandin  and  Nuhn).  The  alveolingual  ele- 
ments arise  from  a  keel  attached  to  the  alveolingual  sulcus  (the  groove 
between  the  floor  of  the  mouth  and  the  alveolar  process  of  the  lower  jaw). 

The  parotid  gland  originates  from  the  buccal  sulcus  in  essentially  the  same 
way  as  the  submaxillary  arises  from  the  lingual  sulcus.  The  anlage  then 
continues  to  grow  through  the  mesenchyme  of  the  cheek  across  the  masseter 
muscle,  the  distal  end  branching  freely  to  form  the  secreting  portion  of  the 
gland.  The  outgrowths  are  at  first  solid,  but  later  become  hollow,  the 
proximal  portion  of  the  original  outgrowth  forming  the  parotid  (Steno's) 
duct,  the  more  distal  portions  forming  the  smaller  ducts  and  terminal  tubules. 

The  histogenetic  changes  in  the  salivary  glands  probably  continue  until  the 
child  takes  solid  food,  when  the  glands  become  of  greater  functional  importance. 
In  the  parotid  gland,  which  is  serous  in  man,  the  original,  undifferentiated 
epithelial  cells  undergo  changes  in  form  and  arrangement  so  that  by  the 
twenty-second  week  the  larger  ducts  are  lined  with  a  two-layered  epithelium, 
the  smaller  ducts  with  a  simple  cuboidal  epithelium,  and  the  terminal  tubules  with 
a  single  layer  of  high  columnar  cells.  The  two-layered  epithelium  in  the  larger 
ducts  persists.  The  ducts  lined  with  the  cuboidal  epithelium  become  the 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       329 


socalled  intermediate  tubules,  the  cells  changing  to  a  flat  type.  The  high 
columnar  cells  of  the  terminal  tubules  become  the  serous  secreting  cells. 

Quite  similar  changes  also  occur  in  the  submaxillary,  but  in  foetuses  of 
eight  to  nine  months  the  crescents  of  Gianuzzi  appear  as  masses  of  darkly 
staining  cells  forming  the  ends  or  sides  of  the  terminal  tubules.  The  crescents 
at  first  border  on  the  lumina,  but  later,  probably  by  a  process  of  evagination, 
come  to  lie  on  the  surface  of  the  tubules. 

The  beginning  of  the  secretory  function  may  be  detected  by  a  diminution  in 
the  affinity  of  the  cells  for  stains. 

The  Pharynx. 

The  pharynx  develops  from  the  cephalic  end  of  the  primitive  gut.  This 
part  of  the  gut  is  primarily  of  uniform  diameter,  is  broadly  attached  by  meso- 
derm  to  the  dorsal  body  wall,  and  ends  blindly  (Fig.  285).  When  the  branchial 
arches  and  grooves  develoo  in  this  (the  cervical)  region,  they  affect  the  gut  as 


Neural  tube 
(brain) 


Maxillary  process 
Mandibular  process 


Heart  -- — . 


, Notochord 


.  Branchial  arches  and 
grooves (pharynx) 


•;--  Lung  groove 


FIG.  294. — Sagittal  section  through  the  head  of  a  human  embryo  of  4.2  mm.  (31-34  days).     His. 

well  as  the  periphery  of  the  body.  The  arches  form  ridges  on  the  surface  of  the 
body  (Fig.  122)  and  at  the  same  time  form  ridges  on  the  wall  of  the  gut.  The 
grooves  form  pockets  which  alternate  with  the  arches  (Fig.  294).  The  pockets 
in  the  pharyngeal  cavity,  or  inner  branchial  grooves,  are  directed  outward 
toward  corresponding  outer  branchial  grooves  (Fig.  287).  The  arches  are 
covered  externally  with  ectoderm,  internally  with  entoderm,  and  are  filled  with 
mesoderm.  Between  the  arches,  or  in  the  grooves,  the  ectoderm  and  entoderm 
are  in  contact  or  nearly  so.  Thus  the  pharynx  is  not  surrounded  by  a  ccelomic 
cavity. 


330  TEXT-BOOK  OF  EMBRYOLOGY. 

Since  the  branchial  arches  develop  in  such  a  way  that  they  are  successively 
smaller  from  the  first  to  the  fourth,  the  pharyngeal  cavity  becomes  funnel- 
shaped  (Fig.  294).  It  also  becomes  somewhat  flattened  in  the  dorso- ventral 
direction,  and  in  the  earlier  stages  when  the  arches  and  grooves  are  fully  formed, 
the  pharynx  constitutes  approximately  one- third  the  entire  gut  (Fig.  285). 
Primarily  the  pharyngeal  cavity  is  separated  from  the  oral  cavity  by  the  pharyn- 
geal membrane  (see  p.  318;  also  Fig.  282).  When  this  ruptures  and  disappears 
(during  the  fourth  week  ?)  the  two  cavities  are  in  open  communication.  What 
point  in  the  adult  represents  the  attachment  of  the  pharyngeal  membrane  is 
not  known;  but  the  glosso-  and  pharyngopalatine  arches  (pillars  of  the  fauces) 
are  usually- considered  as  the  boundary  between  the  mouth  and  pharynx.  The 
caudal  limit  of  the  pharynx  is  the  opening  of  the  larynx  (Figs.  285  and  294). 

Thus  in  the  early  stages  the  general  adult  character  of  the  pharynx  is  es- 
tablished. While  the  branchial  arches  and  grooves  undergo  profound  changes, 
the  pharyngeal  cavity  retains  the  same  relation  to  the  mouth  and  to  the  oeso- 
phagus and  respiratory  tract.  The  cavity  becomes  relatively  shorter,  however, 
and  the  alternating  ridges  and  pockets  in  its  walls  are  lost  as  the  arches  and 
grooves  are  transformed  into  other  structures.  The  metamorphosis  of  the 
arches  and  grooves  is  considered  elsewhere  (p.  145). 

THE  TONSILS. — The  tonsils  arise  in  the  region  of  the  ventral  part  of  the 
second  inner  branchial  groove.  During  the  third  month  the  epithelium 
(entoderm)  grows  into  the  underlying  connective  (mesenchymal)  tissue  in  the 
form  of  a  hollow  bud.  From  this,  secondary  buds  develop,  which  are  at  first 
solid,  but  later  (during  the  fourth  or  fifth  month)  become  hollow  by  a  disappear- 
ance of  the  central  cells  and  open  into  the  cavity  of  the  primary  bud,  thus  form- 
ing the  crypts.  Lymphoid  cells  wander  from  the  neighboring  blood  vessels,  or 
are  derived  directly  from  the  epithelium  (Retterer),  and  with  the  connective 
tissue  form  a  diffuse  lymphatic  tissue  under  the  epithelium  (Fig.  295).  By  the 
eighth  month  the  cells  become  more  numerous  in  places,  and  by  the  third 
month  after  birth  form  distinct  lymph  follicles  with  germinal  centers.  The 
formation  of  follicles  goes  on  slowly  and  is  probably  not  complete  until 
some  time  after  birth. 

The  Lingual  Tonsils. — The  lymphatic  tissue  of  the  tongue  develops  in  rela- 
tion to  the  lingual  glands.  During  the  eighth  month  lymphoid  infiltration 
occurs  around  the  ducts  of  the  glands,  and  the  connective  tissue  acquires  the 
reticular  character.  True  follicles  probably  do  not  appear  until  the  child  is  at 
least  five  years  old. 

The  Pharyngeal  Tonsils. — During  the  sixth  month  small  folds  appear  in  the 
mucous  membrane  of  the  roof  of  the  pharynx  and  become  diffusely  infiltrated 
with  lymphoid  cells.  This  occurs  first  in  the  posterior  part  of  the  roof,  but  later 
(seventh  or  eighth  month)  it  extends  forward  and  along  the  sides  of  the  naso- 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       331 

pharygeal  cavity.  By  the  end  of  foetal  life  the  ridges  become  quite  large. 
Follicles  may  appear  before  birth  or  not  until  one  or  two  years  later.  After 
puberty  the  ridges  almost  completely  disappear,  but  the  adenoid  tissue  remains 
wholly  or  in  part. 

The  bursa  pharyngea  is  an  evagination  from  the  roof  of  the  pharynx  about 
the  upper  border  of  the  superior  constrictor  muscle,  and  is  apparent  in  em- 
bryos of  eleven  weeks.  It  probably  has  no  genetic  relation  to  the  hypophysis. 
Its  significance  is  not  known. 


FIG.  295. — Section  through  the  middle  of  the  developing  tonsil  of  a  human 

embryo  of  5  months.     Stohr. 

6,  Epithelial  buds  (secondary  outgrowths)  from  the  epithelium  lining  the  primary  crypt  (c); 
L,  lymphoid  infiltration  of  the  connective  (mesodermal)  tissue. 

THE  BRANCHIAL  EPITHELIAL  BODIES. 

THE  THYREOID- GLAND. — The  thyreoid  arises,  after  the  manner  of  ordinary 
glands,  as  an  evagination  from  the  epithelium  of  the  pharynx.  It  appears  in 
embryos  of  3  to  5  mm.  as  a  ventral  outgrowth  of  epithelium  in  the  floor  of  the 
pharynx,  at  the  point  where  the  tuberculum  impar  and  the  twro  paired  anlagen 
of  the  tongue  join  (Fig.  296).  This  point  is  the  foramen  caecum  linguae  which 
has  already  been  mentioned  in  connection  with  the  development  of  the  tongue 
(p.  32 1) .  The  evagination  grows  into  the  mesodermal  tissue  in  the  ventral  wall 
of  the  neck,  and  forms  a  transverse  mass  of  epithelium.  The  latter  breaks  up 
into  irregular  cords  of  cells  which,  by  a  further  process  of  budding,  grow  cau- 
dally  along  the  ventral  surface  of  the  larynx.  The  cords  of  cells  are  from  the 
first  surrounded  by  connective  tissue  and  later  also  become  surrounded  by  net- 
works of  capillaries  (Fig.  297).  They  ultimately  break  up  into  smaller  masses 
which  become  hollow  and  form  the  alveoli.  Colloid  secretion  begins  toward 
the  end  of  fcetal  life  or  soon  after  birth. 

As  the  gland  grows  toward  its  final  position  it  becomes  enlarged  laterally  into 
the  two  lateral  lobes,  which  remain  connected  by  the  isthmus  (Fig.  298).  The 
pyramidal  process  represents  either  a  secondary  outgrowth  from  the  isthmus  or 
one  of  the  lobes,  or  a  remnant  of  the  original  connection  with  the  tongue,  that  is, 


332 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  the  thyreo  glossal  duct.  The  duct  usually  disappears  for  the  most  part,  but 
certain  structures  sometimes  found  in  the  adult  in  the  line  of  the  duct  are 
possibly  remnants  of  it.  They  have  been  variously  named,  according  to  their 
position,  accessory  thyreoid  y  suprahyoid,  and  prehyoid  glands  (Fig.  298). 

A  pair  of  structures,  appearing  first  in  embryos  of  8  to  10  mm.,  arise  as 
evaginations  from  the  ventral  ends  of  the  fourth  inner  branchial  grooves.  They 
grow  into  the  mesodermal  tissue  and  then  caudally  along  the  ventro-lateral  side 


Notochord 


Thymus 


Thyreoid 


Jugular  vein 
Vagus  nerve 


Carotid  artery 
Parathyreoid  (epith.  body) 

Thymus  (in.  br.  groove  III) 


Heart 


FIG.  296. — Transverse  section  through  the  region  of  the  3d  branchial  .groove 

of  an  Echidna  embryo.     Maurer. 
i.=  Pharynx,  below  which  are  the  paired  anlagen  of  the  tongue. 

of  the  larynx,  where  they  come  into  close  relation  with  the  lateral  lobes  of  the 
thyreoid  (Fig.  298).  They  have  been  called  the  lateral  thyreoids,  and  acquire 
the  thyreoid  structure. 

Considerable  confusion  has  arisen  in  regard  to  the  lateral  thyreoids.  The  earlier  investi- 
gators held  that  they  were  derived  from  the  fourth  groove  and  united  with  the  medial  portion, 
which  appeared  at  the  foramen  caecum,  to  become  integral  parts  of  the  thyreoid.  Further 
researches  among  the  lower  Vertebrates  led  others  to  deny  that  the  thyreoid  arose  other 
than  as  a  medial  anlage,  and  that  the  so-called  lateral  thyreoids  in  the  embryo  were  the 
postbranchial  bodies  which  never  assumed  the  thyreoid  structure,  but  atrophied  and  dis- 
appeared. More  recently  it  has  been  thought  that,  although  the  postbranchial  bodies  do 
not  function  in  the  lower  Vertebrates,  they  may  in  the  higher  Mammals  and  man  unite  with 
the  medial  thyreoid  and  secrete  colloid. 

The  parathyreoids  or  epithelial  bodies  also  come  into  close  relation  with  the 
thyreoid.  They  arise  as  paired  evaginations  from  the  cephalic  sides  of  the  third 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       333 


and  fourth  grooves,  dorsal  to  the  thymus  and  the  lateral  thyreoid  evaginations 
(Figs.  296  and  299).  As  the  thyreoid  grows  caudally  from  its  point  of  origin, 
these  bodies  come  to  lie  close  to  it  or  may  even  become  embedded  in  it  (Fig.  298). 
They  acquire  a  structure  which  resembles  that  of  the  suprarenal  gland  and  not 


Trachea 


Lateral  lobe 


Capillaries 
Isthmus 


FIG.  297. — Section  of  the  right  half  of  the  thyreoid  gland  of  a  pig  embryo  of  22.5  mm.     Born. 


Accessory  thyroeids 


Accessory  tnyroeids 
(thyreoglossal  duct; 

I 


Carotid  artery 


P.-th. 

Lat.  thyreoid 
(postbr.  body) 


Rignt  subclavian  artery 


Thymus 


Pyramidal  process 

Carotid  artery 
Lateral  thyreoid 
Isthmus 

Lumen  in  thymus 
subclavian  artery 


Arch  of  aorta 

FlG.  298. — Branchial  groove  derivatives  of  a  rabbit  embryo  of  16  mm.    P.-th.,  parathyreoid 
or  epithelial  body.     Verdun,  Bonnet. 

that  of  the  thyreoid.     Their  relation  to  the  latter  organ  seems  to  be  purely 
topographical. 

THE  THYMUS. — The  thymus  appears  in  embryos  of  about  6  mm.  as  an 
entodermal  evagination  from  the  ventral  part  of  the  third  branchial  groove  on 


334  TEXT-BOOK  OF  EMBRYOLOGY. 

each  side  (Fig.  296) .  The  outgrowths  are  at  first  hollow  and  communicate  with 
the  pharyngeal  cavity;  later  they  become  solid  and  (in  embryos  of  14  mm.)  lose 
their  connection  with  the  parent  epithelium.  They  elongate  and  grow  caudally 
in  the  mesodermal  tissue  until  (in  embryos  of  16  mm.)  their  caudal  ends  lie 
ventral  to  the  carotid  arteries  (Fig.  298).  In  embryos  of  29  mm.  their  caudal 
ends  rest  upon  the  cephalic  surface  of  the  pericardium,  their  cephalic  ends 
reaching  to  the  isthmus  of  the  thyreoid.  The  two  parts  eventually  fuse  to  a 
considerable  extent,  but  the  gland  as  a  whole  always  consists  of  two  distinct 
lobes. 

The  gland  continues  to  enlarge,  at  the  same  time  becoming  lobulated  by  the 
ingrowth  of  connective  tissue,  until  the  child  is  two  or  three  years  old.  At  this 
time  it  is  situated  in  the  anterior  mediastinum,  usually  in  the  medial  line.  After 
this  it  begins  to  atrophy  and  becomes  a  mass  of  fibrous  and  fatty  tissue  through 
the  growth  of  the  interlobular  septa  and  their  encroachment  upon  the  lobules. 
The  classical  view  that  the  thymus  begins  to  atrophy  after  the  second  or  third 
year  and  is  quite  degenerated  in  the  adult  has  recently  been  somewhat  offset 


Lat.  thyreoid 
(postbr.  body) 

FIG.  299. — Diagram  of  the  branchial  groove  derivatives  in  man.     Verdun. 

by  the  view  that  comparatively  slight  changes  take  place  in  it  until  puberty. 
According  to  the  latter  view,  degeneration  goes  on  after  puberty  at  a  rate  which 
varies  widely  in  different  individuals,  and  the  thymus  may  persist  as  a  functional 
organ  up  to  the  age  of  sixty  years. 

The  histogenesis  of  the  thymus  has  been  a  subject  of  much  study  and  con- 
troversy, not  only  in  regard  to  its  origin,  but  also  in  regard  to  its  change  from 
an  epithelial  to  a  lymphoid  structure  and  the  regressive  changes  in  the  latter. 
It  has  almost  certainly  been  proven  to  be  of  entodermal  origin.  It  is  at  first  an 
epithelial  mass  which  later  becomes  broken  up  into  lobules  by  the  ingrowth  of 
connective  tissue.  In  regard  to  the  histological  changes  which  it  undergoes, 
the  older  views  are  in  general  that  a  "  pseudomorphosis "  takes  place;  that  is, 
the  epithelial  elements  are  replaced  by  lymphoid  cells  which  wander  in  from 
the  neighboring  blood  vessels,  HassalPs  corpuscles  being  remnants  of  the 
epithelium.  Later  other  investigators  looked  upon  the  changes  as  a  "  transfer- 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       335 

mation,"  asserting  that  the  epithelial  cells  were  transformed  into  lymphoid 
cells  in  situ,  and  that  Hassall's  corpuscles  were  remnants  of  epithelium  and 
disintegrating  blood  vessels.  Some  went  even  so  far  as  to  assert  that 

the  thymus  was  the  first  place  of  origin  of 
the  leucocytes.  More  recent  researches 
furnish  very  strong  evidence  that  no  lymph- 
oid cells  are  derived  from  the  epithelial 
cells  (Maximow),  but  that  the  epithelium  is 
transformed  into  the  reticular  tissue  of  the 
thymus,  in  which  the  lymphoid  cells  undergo 
mitotic  division,  Hassall's  corpuscles  possibly 
representing  compressed  parts  of  the  reticu- 
lum  (Hammar)  (Fig.  300). 

THE    GLOMUS    CAROTICUM. — The  early 
formation  of  the  glomus  caroticum  (carotid 
FIG.  300.— Hassall's  corpuscle  from      gland)  has  not  been  observed  in  the  human 
^mnr^lr.1"11311^'"50'      embryo.       From     observations     on     lower 

animals  it  has  not  been  made  clear  whether 

it  is  derived  from  the  entoderm  of  a  branchial  groove  or  from  the  adventitia 
of  the  carotid  artery. 

The  (Esophagus  and  Stomach. 

THE  (ESOPHAGUS. — When  the  primitive  gut  becomes  differentiated  into 
distinct  regions  (p.  317),  the  cesophageal  region  forms  a  comparatively  short 
tube,  of  uniform  diameter,  extending  from  the  pharynx  to  the  stomach  (Fig. 
285).  In  embryos  of  about  3  to  4  mm.  the  anlage  of  the  respiratory  system 
arises  from  the  cephalic  end  of  the  tube  (see  p.  360).  The  latter  is  lined  with 
entoderm  and  broadly  attached  to  the  dorsal  body  wall  by  mesoderm  (Fig.  285). 
During  later  stages  it  becomes  relatively  longer  as  the  heart  recedes  into  the 
thorax  (p.  245),  but  maintains  its  uniform  diameter. 

Further  development  produces  no  marked  changes  in  the  relative  position 
of  the  oesophagus.  It  remains  broadly  attached  to  the  dorsal  body  wall 
throughout  the  life  of  the  individual.  In  other  words,  there  is  never  a  distinct 
mesentery.  The  entoderm  gives  rise  to  the  epithelial  lining  and  the  glands,  the 
surrounding  mesoderm  to  the  connective  tissue  and  muscular  coats. 

THE  STOMACH. — The  anlage  of  the  stomach  can  br  recognized  in  embryos 
of  about  5  mm.  as  a  slight  spindle-shaped  enlargement  of  the  primitive  gut  a 
short  distance  cranial  to  the  yolk  stalk  (Fig.  284).  The  dilatation  goes  on  more 
rapidly  on  the  dorsal  than  on  the  ventral  side,  thus  producing  the  greater  and 
lesser  curvature  respectively.  The  greater  curvature  is  attached  to  the  dorsal 
body  wall  by  the  dorsal  mesogastrium  which  is  a  part  of  the  common  mesentery. 


336 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  lesser  curvature  is  connected  with  the  ventral  body  wall  by  the  ventral 
mesogastrium  (Fig.  301). 

In  further  development,  apart  from  histogenesis,  the  greater  curvature 
becomes  much  more  prominent  and  the  organ  as  a  whole  changes  its  position, 
the  latter  process  beginning  in  embryos  of  12  to  14  mm.  The  cephalic  (car- 
diac) end  moves  toward  the  left  side  of  the  body,  the  pyloric  end  toward  the 
right  At  the  same  time  the  stomach  rotates,  the  greater  curvature  turning 


Ventral  mesogastrium  — — 


—-—Aorta 


Spleen 
""  Dorsal  mesogastrium 

—  Coeliac  artery 

—  Pancreas 

Sup.  mesenteric  artery 


r Common  mesentery 


Inf.  mesenteric  artery 

Hind-gut  (rectum) 
FIG.  301. — Gastrointestinal  tract  and  mesenteries  of  a  human  embryo  of  6  weeks.     Toldt. 


Caecum 


caudally  from  its  dorsal  position  and  the  lesser  curvature  cranially  from  its 
ventral  position.  The  result  is  that  the  organ  comes  to  lie  in  an  approximately 
transverse  position  in  the  body,  with  the  cardiac  end  to  the  left,  the  pyloric  end 
to  the  right,  the  greater  curvature  directed  caudally,  and  the  lesser  curvature 
directed  cranially  (compare  Figs.  285  and  301  with  Figs.  314  and  342).* 

*  These  changes  may  be  more  easily  understood  if  the  student  will  hold  a  closed  book  in  the 
sagittal  plane  in  front  of  him,  with  the  back  of  the  book  toward,  and  the  open  edge  away  from  him. 
The  back  represents  the  greater  curvature,  the  open  edge  the  lesser  curvature.  The  upper  end  of 
the  book  represents  the  cardiac  end  of  the  stomach,  the  lower  end  the  pylorus.  Turn  the  upper 
(cardiac)  end  to  the  left,  the  lower  (pyloric)  end  to  the  right,  at  the  same  time  allowing  the  back  of 
the  book  (the  greater  curvature)  to  drop  downward  on  the  side  toward  the  body.  The  changes  in 
the  position  of  the  book  represent  the  changes  in  the  position  of  the  developing  stomach. 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       337 

It  is  obvious  that  the  lower  end  of  the  oesophagus  is  carried  toward  the  left 
side  of  the  body  with  the  cardiac  end  of  the  stomach,  and  at  the  same  time 
twisted  so  that  the  side  which  originally  faced  the  left  comes  to  face  ventrally. 
The  changes  in  the  mesentery  which  accompany  the  changes  in  the  stomach 
are  described  elsewhere  (p.  378). 

The  torsion  of  the  stomach  also  produces  an  asymmetrical  condition  of  the 
vagi  nerves.  The  latter  reach  the  stomach  before  it  changes  its  position.  As 
the  changes  take  place,  the  left  nerve  is  carried  around  to  the  left  and  ventrally 
so  that  in  the  adult  it  passes  through  the  diaphragm  ventral  to  the  oesophagus 
and  extends  over  the  ventral  surface  of  the  stomach.  The  right  nerve  passes 
over  the  dorsal  surface  of  the  stomach. 

The  Intestine. 

When  the  primitive  gut  is  differentiated  into  recognizable  regions  (p.  317) 
the  intestinal  region  forms  a  simple  tube,  of  uniform  diameter,  extending  from 
the  stomach  to  the  caudal  end  of  the  embryo  where  it  ends  blindly.  The  yolk 
stalk  is  attached  to  the  intestine  a  short  distance  from  the  stomach.  Near  the 
caudal  end  the  allantoic  duct  arises  (p.  114).  The  lumen  of  the  yolk  stalk  and 
of  the  allantoic  duct  is  continuous  with  that  of  the  intestine  (Fig.  285).  In 
embryos  of  2  to  3  mm.  the  liver  anlage  arises  from  the  ventral  side  of  the 
intestine  near  the  stomach,  that  is,  from  that. part  of  the  intestine  which  is  to 
become  the  duodenum.  In  embryos  of  3  to  4  mm.  the  pancreas  anlage  arises 
in  the  same  region,  in  part  from  the  liver  evagination  and  in  part  from  the  dorsal 
side  of  the  intestine  (Fig.  285). 

The  intestine  as  a  whole  is  suspended  in  the  abdominal  cavity  by  the  dorsal 
mesentery  which  is  attached  to  the  dorsal  body  \vall  and  which  is  continuous 
with  the  dorsal  mesogastrium.  A  ventral  mesentery,  continuous  with  the 
ventral  mesogastrium,  is  present  only  at  the  cephalic  end  of  the  duodenum 
(Fig.  301). 

The  further  development  of  the  intestine,  apart  from  histogenesis,  consists 
very  largely  of  the  formation  of  loops  and  coils,  due  to  an  enormous  increase  in 
the  length  of  the  tube.  The  abdominal  cavity  at  the  same  time  enlarges  to 
accommodate  the  increased  bulk.  As  the  stomach  changes  its  position  (p.  336), 
the  duodenum  comes  to  lie  obliquely  across  the  body  and  forms  a  curve  with  the 
concavity  directed  dorsally  (Fig.  301).  The  rest  of  the  intestine  forms  a  loop 
which  extends  ventrally  and  caudally  as  far  as  the  umbilicus.  The  arms  of  the 
loop  are  almost  parallel  and  the  cephalic  arm  lies  a  little  to  the  left  of  the  caudal. 
The  apex  of  the  loop  extends  into  the  umbilical  coelom  and  is  attached  to  the  yolk 
stalk.  From  the  dorsal  end  of  the  caudal  arm  the  intestine  extends  directly 
to  the  caudal  end  of  the  body  (Fig.  301). 

Soon  after  the  loop  is  formed  a  small  evagination  appears  on  its  caudal  arm, 
not  far  from  the  apex.  This  is  the  anlage  of  the  cacum  and  marks  the  bound- 


338  TEXT-BOOK  OF  EMBRYOLOGY. 

ary  between  the  small  and  large  intestine  (Fig.  301).  At  this  stage,  therefore, 
all  the  great  divisions  of  the  intestinal  tract  are  distinguishable,  viz. :  the  duodenum 
with  the  ducts  of  the  liver  and  pancreas;  the  mesenterial  small  intestine  with  the 
yolk  stalk;  and  the  colon  extending  from  the  caecum  to  the  caudal  end.  There 
are,  however,  practically  no  differences  between  the  regions,  either  in  structure 
or  in  size. 

In  further  development  the  duodenum  comes  to  lie  more  nearly  transversely 
across  the  body,  thus  assuming  its  adult  position.  Its  mesentery  fuses  with  the 
peritoneum  of  the  dorsal  body  wall  and  the  duodenum  thus  becomes  a  fixed 
portion  of  the  intestinal  tract  (p.  380;  also  Fig.  339).  It  enlarges  a  little  more 


Portal  vein    - 


Foramen  of 
Winslow 


FIG.  302. — Reconstruction  of  the  liver  and  intestine  of  a  human  embryo  of  17  mm.     Mall. 

G.B.,   gall  bladder;  H.  V.,  hepatic   vein;  U.V.,  umbilical  vein;   1-6,  primary  bends  in  the   long 

intestinal  loop;  i  represents  the  duodenum. 

rapidly  than  the  rest  of  the  small  intestine  and  acquires  a  greater  diameter.  In 
embryos  of  12  to  13  mm.  the  lumen  becomes  obliterated  by  an  overgrowth  of  the 
mucous  membrane  caudal  to  the  ducts  of  the  liver  and  pancreas.  In  embryos 
of  about  15  mm.,  however,  the  lumen  reappears.  It  seems  difficult  to  find  a 
cause  for  this  peculiar  growth  of  the  mucosa. 

Very  shortly  after  the  formation  of  the  long  loop  in  the  intestine,  six  bends 
become  recognizable  in  the  portion  between  the  stomach  and  the  apex  of  the 
loop  (Fig.  302).  These  bends  later  form  distinct  loops  which  are  destined  to 
become  definite  parts  of  the  small  intestine.  The  first  loop  is  the  duodenum, 
the  development  of  which  has  already  been  considered,  and  which  maintains 
practically  its  original  position.  The  other  five  loops  continue  to  elongate  and 
form  secondary  loops,  all  of  which  push  their  way  into  the  umbilical  coelom 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       339 


where  they  remain  until  the  embryo  reaches  a  length  of  40  mm.  (compare  Figs. 
303  and  304) .  Then  they  return  very  quickly  to  the  abdominal  cavity  proper. 

After  their  return,  the  primary  loops,  with  the  secondary  loops  derived  from 
them,  come  to  occupy  fairly  constant  positions.  The  second  and  third  move 
to  the  left  upper  part  of  the  abdominal  cavity;  the  fourth  crosses  the  medial 
line  and  occupies  the  right  upper  part.  The  fifth  crosses  back  and  lies  in  the 
left  iliac  fossa;  the  sixth  lies  in  the  pelvis  and  lower  part  of  the  abdominal 
cavity  (Fig.  305). 

Certain  variations  may  occur  but  are  usually  not  considered  as  abnormal. 
The  most  frequent  variation  is  one  in  which  the  fourth  coil,  along  with  the 


FIG.  303. — Reconstruction  of  the  stomach  and  intestine  of  a  human  embryo  of  28  mm.     Mall. 

The  numbers  are  placed  on  the  coils  derived  from  the  primary  bends  as  shown  in 

Fig.  302;  i  represents  the  duodenum. 

second  and  third,  lies  on  the  left  side,  its  usual  position  on  the  right  being  oc- 
cupied by  the  ascending  colon.  Xot  uncommonly  the  positions  of  the  fourth 
and  the  second  and  third  are  reversed.  Less  commonly  extra  loops  are  formed. 

Usually  the  proximal  part  of  the  yolk  stalk  disappears  during  fcetal  life.  In 
a  few  cases,  however,  it  persists  as  a  blind  sac  of  variable  length,  known  as 
MeckePs  diverticulum  (see  also  p.  113). 

Even  before  the  loops  return  to  the  abdominal  cavity  the  colon  or  large 
intestine  increases  in  diameter  more  rapidly  than  the  small  intestine.  After 
the  return,  the  caecum  is  carried  across  to  the  right  side  and  comes  to  lie  just 
caudal  to  the  liver.  From  the  caecum  the  colon  extends  across  the  abdominal 


340 


TEXT-BOOK  OF  EMBRYOLOGY. 


cavity,  ventral  to  the  duodenum,  forming  the  transverse  colon.  It  then  de- 
scends on  the  left  side  as  the  descending  colon  which  passes  over  into  the  sigmoid 
colon  (Fig.  337).  The  transverse,  the  descending  and  the  sigmoid  portions  of 
the  colon  are  recognizable  in  the  third  month.  Up  to  the  time  of  birth  the 
sigmoid  portion  is  disproportionately  long;  after  birth  the  other  portions 


FIG.  304. — Drawing  from  a  reconstruction  of  a  human  embryo  of  24  mm.     Matt. 
The  intestinal  coils  lie  for  the  most  part  in  the  umbilical  ccelom.     C,  caecum;  K,  kidney;  L,  liver. 
S,  stomach;  S.  C.,  suprarenal  gland;  W,  mesonephros;  12,  twelfth  thoracic  nerve;  5,  fifth 
lumbar  nerve. 

grow  relatively  faster.  After  the  fourth  month  the  portion  to  which  the  caecum 
is  attached  grows  downward  in  the  right  side  of  the  abdominal  cavity,  thus  form- 
ing the  ascending  colon  (Fig.  342). 

The  caecum,  which  appears  in  very  early  stages  as  an  evagination  at  the 
junction  of  the  small  and  large  intestines,  for  a  time  continues  to  increase  uni- 
formly in  size.  Then  the  proximal  end  increases  more  rapidly  than  the  distal, 
and  forms  the  caecum  of  adult  anatomy.  The  distal  end,  failing  to  keep  pace 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       341 

in  development,   remains  more  slender  and  forms  the  vermiform  appendix 
(Fig.  305). 

As  has  already  been  mentioned,  the  primitive  gut  ends  blindly  in  the  caudal 
end  of  the  embryo  (Fig.  284).  The  anal  opening  is  a  secondary  formation. 
On  the  ventral  side  of  the  caudal  end  of  the  body  there  is  formed  a  depression 
known  as  the  anal  pit.  The  mesoderm  at  the  bottom  of  the  pit  becomes  thin- 
ner until  the  ectoderm  comes  in  contact  with  the  entoderm  on  the  ventral  side 
of  the  gut,  thus  forming  the  anal  membrane.  The  area  of  contact  is  not  at  the 


FIG.  305.— Drawing  from  a  model  of  the  small  intestine  in  the  adult.     Ventral  view.     Mall. 

The  intestinal  coils  are  shown  in  the  usual  relative  position.     The  numbers  indicate  the  coils  derived 

from  the  primary  bends  in  the  foetus  as  shown  in  Figs.  302  and  303. 

extreme  end  of  the  gut,  but  a  short  distance  toward  the  allantoic  duct.  In  the 
meantime,  the  urogenital  ducts  come  to  open  into  that  portion  of  the  gut  which 
lies  just  cranial  to  the  anal  membrane.  The  gut  enlarges  in  this  region  to 
form  the  cloaca.  The  latter  becomes  separated  by  the  urorectal  fold  into  a 
dorsal  portion,  the  rectum,  and  a  ventral  portion,  the  urogenital  sinus  (Figs.  361 
and  363).  At  about  the  time  of  separation  (embryos  of  about  14  mm.  or 
thirty-six  to  thirty-eight  days)  the  anal  membrane  ruptures  and  the  anal  open- 


342 


TEXT-BOOK  OF  EMBRYOLOGY. 


ing  is  formed.     The  portion  of  the  gut  caudal  to  the  anus,  known  as  the  caudal 
gut,  normally  disappears. 

Histogenesis  of  the  Gastrointestinal  Tract. 

The  wall  of  the  primitive  gut  is  composed  of  two  layers — the  entoderm  which 
lines  the  lumen,  and  the  splanchnic  mesoderm  which  borders  on  the  ccelom  or  body 
cavity.  While  the  germ  layers  are  still  flat,  the  entoderm  is  a  single  layer  of  flat 
cells  with  bulging  nuclei,  but  after  the  closure  of  the  gut  the  cells  become  col- 
umnar. The  splanchnic  mesoderm  is  composed  of  two  layers — the  mesothe- 
lium  bordering  on  the  ccelom,  the  cells  of  which  gradually  change  from  flat 


Mesentery 


Epithelium 


Stroma 


Mesothelium 


Long. 
Trans.  J 


muscle 


FIG.  306. — Transverse  section  of  the  small  intestine  of  a  pig  embryo  of  32  mm.     Bonnet. 

to  rather  high,  and  a  number  of  indifferent,  branching  mesenchymal  cells 
lying  between  the  mesothelium  and  entoderm.  The  entoderm  is  destined  to 
give  rise  to  the  general  epithelial  lining  of  the  gastrointestinal  tract  and  to  all 
the  glands  connected  with  it.  The  mesothelium  around  the  gut  forms  a  part  of 
the  general  mesothelial  lining  of  the  ccelom,  its  cells  apparently  changing  back 
to  a  flat  type.  The  mesenchymal  tissue  is  destined  to  give  rise  to  all  the  con- 
nective tissue  and  smooth  muscle  of  the  tract.  The  circular  layer  of  muscle 
appears  first,  the  longitudinal  next,  both  appearing  during  the  third  and  fourth 
months,  and  last  of  all  the  muscularis  mucosae  (Fig.  306). 

THE  Mucous  MEMBRANE. — The  mucous  membrane  is  formed  by  the 
epithelium  (entoderm)  and  the  subjacent  mesenchymal  tissue.     In  its  develop- 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       343 

ment  there  are  two  factors  to  be  considered:  (i)  The  formation  of  folds  to  in- 
crease the  absorbing  surface  and  (2)  the  formation  of  secreting  organs  or  glands. 
As  to  the  relation  between  these  two  factors  there  is  a  difference  of  opinion. 
Some  hold  that  both  kinds  of  structures  are  the  result  of  the  same  formative 
process,  that  is,  that  the  glands  are  simply  the  depressions  or  pits  formed  by  the 
intersection  of  folds  at  various  angles,  and  that  the  folds  are  produced  primarily 
by  the  growth  of  the  epithelium  and  mesenchymal  tissue  into  the  lumen  of  the 
gut.  Others  maintain  that  although  the  folds  may  be  produced  by  the  growth 
of  the  epithelium  and  mesenchymal  tissue  into  the  lumen,  the  glands  arise  as 
independent  growths  of  the  epithelium  into  the  subjacent  tissue.  The  latter 

view  is  supported  by  the  fact  that  in 
some  Amphibia  the  glands  appear  before 
the  folds  (Fig.  307).  Recent  work  on 
Mammals  also  favors  this  view. 

The  development  of  the  folds  and 
glands  begins  in  the  different  parts  of  the 
gastrointestinal  tract  at  different  times. 
It  begins  first  in  the  stomach,  then  in  the 

FIG.  307. — Section  through  the  wall  of  the        .        .  .  .  .  .     . 

stomach  of  a  frog  embryo.    Ep.,  Epi-     duodenum,  then  in  the  colon,  and  then 
theiium,  with  glands;  s«fo».  submucosa;     j      the   jejunum   whence    it    progresses 

Muse.,  muscle  layer.     Ratner.  J  J 

slowly  into  the  ileum.  In  the  stomach 

it  is  uncertain  whether  the  crypts  and  glands  are  depressions  left  among 
projections  of  the  mucous  membrane,  or  the  glands  represent  evaginations  of 
the  epithelium  into  the  underlying  tissue.  In  the  case  of  the  large  intestine 
the  same  uncertainty  exists.  If  the  so-called  glands  are  depressions  among 
villous  projections  that  grow  into  the  lumen  of  the  intestine,  they  are  not  true 
glands  from  an  embryological  point  of  view. 

Studies  of  the  development  of  the  mill  in  the  human  small  intestine  have  led 
to  the  conclusion  that  they  are  formed  primarily  as  growths  of  the  mucosa  into 
the  lumen.  In  embryos  of  19  mm.  the  mucosa  of  the  cephalic  end  is  thrown 
into  a  number  of  longitudinal  folds  (Fig.  308).  These  then  develop  pro- 
gressively toward  the  caudal  end.  Beginning  in  embryos  of  50  to  60  mm.  the 
longitudinal  folds  become  broken  transversely  into  conical  structures,  the 
villi.  The  intestinal  crypts  (of  Lieberkuhn)  possibly  represent  outgrowths  of 
the  epithelium  from  the  bottoms  of  the  intervillous  spaces.  The  duodenal 
(Brunner's)  glands  are  possibly  to  be  considered  as  a  continuation  of  the  pyloric 
glands  of  the  stomach.  They  apparently  grow  as  evaginations  from  the 
intervillous  crypts. 

The  epithelial  lining  of  the  gastrointestinal  tract  is  from  the  beginning  a 
single  layer  of  cells,  although  the  individual  cells  are  altered  in  shape  and 
structure  and  acquire  different  functions  in  different  regions.  There  is  still 


344 


TEXT-BOOK  OF  EMBRYOLOGY. 


some  dispute  as  to  whether  the  mucous  cells  are  continuously  being  derived 
from  the  other  epithelial  cells  or,  when  once  formed,  reproduce  themselves  by 
mitosis.  As  a  matter  of  fact,  mitosis  has  been  observed  in  the  mucous  cells  of 
the  stomach. 


FiG.  308. — From  a  reconstruction  of  the  small  intestine  of  a  human  embryo  of  28  mm.,  showing  the 
longitudinal  ridges  which  eventually  become  broken  transversely  to  form  the  villi.     Berry. 

THE  LYMPH  FOLLICLES. — In  the  development  of  the  lymph  follicles  in  the 
gastrointestinal  tract  the  same  question  arises  as  in  the  case  of  the  tonsils  and 
thymus.  Are  the  lymphoid  cells  of  mesodermal  or  of  entodermal  (epithelial) 


a 


— -^ 


FIG.  309.— Sections  through  the  wall  of  the  caecum  of  (a)  a  rabbit  2|  days  and  (6)  5  days  after 
birth,  showing  the  development  of  the  lymph  follicles.  /.  Lymphoid  infiltration  in  the  stroma; 
r,  wandering  cells  in  the  epithelium;  z,  lymphoid  cells  in  the  core  of  a  villus.  Stohr. 

origin?  Evidence  at  present  favors  the  mesodermal  origin.  In  the  case  of 
Peyer's  patches,  collections  of  lymphoid  cells  appear  near  the  blood  vessels  in 
the  stroma  and  neighboring  parts  of  the  submucosa.  These  increase  in  extent, 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       345 


the  lymphoid  cells  dividing  actively,  and  grow  into  the  bases  of  some  of  the 
villi  and  deeper  into  the  submucosa  (Fig.  309).  Germinal  centers  appear  in 
many  of  the  follicles,  and  the  surrounding  stroma  becomes  densely  infiltrated 
with  the  lymphoid  cells.  Individual  follicles  may  develop,  in  the  manner 
described,  in  any  part  of  the  gastrointestinal  tract.  The  appendix  especially  is 
the  seat  of  extensive  lymphatic  tissue  formation.  It  is  stated  in  the  section  on 
the  lymphatic  system  that  lymph  glands  may  arise  at  any  time  in  any  region  as 
the  result  of  unusual  conditions  (p.  282),  and  this  also  holds  true  in  the  case  of 
lymph  follicles  in  the  digestive  tract. 

The  Development  of  the  Liver. 

The  liver  is  the  first  gland  of  the  digestive  tract  to  appear.  In  embryos  of 
about  3  mm.  a  longitudinal  ridge-like  evagination  develops  from  the  entoderm 
on  the  ventral  side  of  the  gut  a  short  distance  caudal  to  the  stomach,  that  is,  in 


Myotome 
Aorta 

Post,  cardinal  vein 
Coelom 


Upper  limb  bud 
Dorsal  mesentery 

Duodenum 
Liver 


Omphalomesenteric  vein 
Umbilical  vein 

Heart 


FIG.  310. — Transverse  section  of  a  human  embryo  of  5  mm.,  showing  the  liver  evagination  and  the 
breaking  up  of  the  omphalomesenteric  veins  by  the  hepatic  cylinders.     Photograph. 

the  duodenal  portion  of  the  gut  (Figs.  285,  310,  311).  The  cephalic  part  of  the 
evagination  is  solid  and,  being  destined  to  give  rise  to  the  liver  proper,  is  called  the 
pars  hepatica.  The  caudal  part  is  hollow,  its  cavity  being  continuous  with  the 
lumen  of  the  gut,  and  is  destined  to  give  rise  to  the  gall  bladder,  whence  it  is 
called  the  pars  cystica.  Beginning  at  both  the  cephalic  and  caudal  ends,  the 
evagination  as  a  whole  becomes  constricted  from  the  gut  until  (in  embryos  of 
about  8  mm.)  its  only  connection  with  the  latter  is  a  narrow  cord  of  cells  which 


346  TEXT-BOOK  OF  EMBRYOLOGY, 

is  the  anlage  of  the  ductus  choledochus.  The  pars  hepatica  by  this  time  has 
enlarged  considerably  and  remains  attached  to  the  ductus  choledochus  by  a 
short  cord  of  cells,  the  anlage  of  the  hepatic  duct.  The  pars  cystica  has  also 
become  larger,  its  distal  portion  being  somewhat  dilated,  and  is  connected  with 
the  ductus  choledochus  by  the  anlage  of  the  cystic  duct  (Figs.  312  and  313). 
The  pars  cystica  grows  into  the  ventral  mesentery  and  thus  becomes  sur- 
rounded by  mesodermal  tissue.  The  proximal  portion  continues  to  elongate  to 
form  the  cystic  duct  and  the  distal  portion  becomes  larger  and  more  dilated  to 
form  the  gall  bladder. 


D.  pan. 


V.  pan. 

^%fa       .^^^..^^^^^v 

D.ch. 

H.du. 


G.bl. 


FIG.  311. — From   a  model  of  the  duodenum  and  the  primary  evaginations  of  the 

liver  and  pancreas  in  a  5  mm.  sheep  embryo.     Stoss. 

D.pan.,  Dorsal  pancreas;  Du.,  duodenum;  D.  ch.,  ductus  choledochus;  G.  bl.,  gall 
bladder;  H.  du.,  hepatic  duct. 

The  pars  hepatica,  or  anlage  of  the  liver  proper,  also  grows  into  the  ventral 
mesentery,  thus  becoming  surrounded  by  mesodermal  tissue.  As  stated  in 
connection  with  the  development  of  the  diaphragm,  the  portion  of  the  mesen- 
tery into  which  the  liver  grows  is  involved  in  the  formation  of  the  septum 
transversum  (p.  374).  Thus  the  developing  liver  becomes  enclosed  in  the 
septum  (Fig.  330).  The  mesodermal  tissue  gives  rise  to  the  fibrous  capsule  of 
Glisson  and  to  the  small  amount  of  connective  tissue  within  the  gland. 

Although  the  liver  develops  as  a  series  of  outgrowths  from  the  original 
evagination,  there  are  certain  features  in  its  development  which  distinguish  it 
from  glands  in  general.  The  outgrowths  come  in  contact  with  the  omphalomes- 
enteric  veins  which  are  situated  in  the  ventral  mesentery  (p.  260).  They  push 
their  way  into  and  through  the  veins,  breaking  them  up  into  smaller  channels 
(Fig.  310).  They  anastomose  freely  with  one  another,  and  the  veins  send  off 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       347 


branches  which  circumvent  them.  Thus  there  is  formed  a  network  of  trabec- 
ulae  of  liver  cells,  called  hepatic  cylinders,  the  meshes  of  which  are  filled  with  blood 
vessels.  Therefore  the  liver  is  distinguished  from  other  glands  in  general  in 


Stomach 


Left  hep. 
duct 


[—  Dors,  pancreas 


'A Vent,  pancreas 


Duodenum 


FIG.  312. — From  a  reconstruction  of  the  anlagen  of  the  liver  and  pancreas  and  a  part  of  the 
stomach  and  duodenum  of  a  human  embryo  of  4  weeks.     Felix. 

that  the  hepatic  cylinders,  which  are  comparable  with  the  smaller  ducts  and 
terminal  tubules  of  other  glands,  anastomose,  and  in  that  the  blood  vessels  are 
broken  up  by  the  growth  of  these  cylinders. 


•4 


FIG.  313. — From  a  reconstruction  of  the  anlagen  of  the  liver  and  pancreas  and  the  stomach 

of  a  human  embryo  of  8  mm.     Hammar. 

D.P.,  Dorsal   pancreas;    Du.,  duodenum;    D.  V.,  ductus  venosus;    G.B.,  gall   bladder; 
R.I.,  right  lobe  of  liver;  £.,  stomach;  V.P.,  ventral  pancreas. 

This  mode  of  development  establishes  what  is  known  as  a  sinusoidal  circulation,  which 
differs  from  the  ordinary  capillary  circulation.  The  sinusoids  are  produced  by  the  growth 
of  the  trabeculse  of  the  developing  organ  into  large  vessels  and  the  breaking  up  of  the  latter 


348 


TEXT-BOOK  OF  EMBRYOLOGY, 


into  smaller  vessels.  It  is  obvious  that  a  sinusoidal  circulation  is  purely  venous  or  purely 
arterial.  Furthermore,  development  of  this  nature  leaves  comparatively  little  connective 
tissue  within  the  gland,  another  feature  characteristic  of  the  liver. 

All  the  blood  carried  to  the  liver  by  the  omphalomesenteric  veins  must 
follow  the  tortuous  course  of  the  sinusoids  before  being  collected  again  and 
passed  on  to  the  heart.  When  the  umbilical  veins  come  into  connection  with 
the  liver  they  also  join  in  the  sinusoidal  circulation.  Subsequently,  however,  a 
more  direct  channel — the  ductus  venosus — is  established  and  persists  for  a 


Right  side 


Suprarenal  glands 
Mesonephros 


Dorsal  mesogastrium 
(greater  omentum) 

Stomach 

Ventral  mesogastrium 
(lesser  omentum) 


Liver 


Left  side 


FlG.  314. — Tranverse  section  of  a  14  mm.  pig  embryo,  through  the  region  of  the  stomach. 
Photograph.     The  arrow  points  into  the  bursa  omentalis. 

short  time.  This  is  probably  due  to  the  large  volume  of  blood  brought  in  by 
the  umbilical  veins.  Finally  the  ductus  venosus  disappears  and  the  sinusoidal 
circulation  remains  as  the  permanent  form.  (For  the  development  of  the  veins 
in  the  liver  see  p.  259.) 

The  lobes  of  the  liver  develop  in  a  general  way  in  relation  to  the  great 
venous  trunks  which  at  one  time  or  another  pass  into  or  through  the  gland. 
The  anlage  of  the  organ  grows  into  the  ventral  mesentery,  subsequently  be- 
coming enclosed  in  the  septum  transversum.  In  so  doing  it  encounters  the 
omphalomesenteric  veins,  and  forms,  in  relation  to  the  latter,  two  incompletely 
separated  parts  which  have  been  called  the  dorso-lateral  lobes.  When  the 
umbilical  veins  enter  the  liver  a  more  ventral,  medial  mass  is  formed.  This 
becomes  incompletely  separated  into  two  parts  which  give  rise  to  the  permanent 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       349 

right  and  left  lobes.  The  right  becomes  the  larger.  The  right  umbilical  vein 
loses  its  connection  with  the  liver  (p.  261).  After  birth  the  left,  which  lies  be- 
tween the  right  and  left  lobes,  degenerates  into  the  round  ligament  of  the  liver, 
The  other  lobes  arise  secondarily  as  outgrowths  from  the  right  primary  dorso- 
lateral  lobe,  the  caudate  (lobe  of  Spigelius)  from  its  inner  (medial)  surface, 
the  quadrate  from  its  dorsal  surface. 

The  liver  as  a  whole  grows  rapidly  and  by  the  second  month  is  relatively 
large.  During  the  third  month  it  fills  the  greater  part  of  the  abdominal  cavity. 
After  the  fifth  month  it  grows  less  rapidly  and  the  other  intraabdominal  organs 
overtake  it,  so  to  speak,  although  at  birth  it  forms  one-eighteenth  the  total 
weight  of  the  body.  After  birth  it  actually  diminishes  in  size.  The  right  lobe 
is  from  the  beginning  larger  than  the  left,  and  after  birth  the  predominance 
increases. 

His  to  genesis  of  the  Liver. — The  hepatic  part  (pars  hepatica)  of  the 
liver  anlage  is  derived  from  the  entodermal  lining  of  the  gut  and  constitutes  a 
mass  of  cells  with  no  lumen.  From  this  mass,  solid  bud-like  evaginations  grow 
into  the  mesentery,  break  up  the  omphalomesenteric  veins  into  smaller  channels 
and  form  trabeculae,  or  hepatic  cylinders  (p.  347).  The  latter  anastomose 
freely  with  one  another  and  are  composed  of  polyhedral,  darkly  staining  cells 
with  vesicular  nuclei  (Fig.  315,  A).  Lumina  begin  to  appear  in  the  cylinders 
about  the  fourth  week  as  small  cavities  which  communicate  with  the  cavity  of 
the  gut. 

The  hepatic  cylinders  are  the  forerunners  of  the  hepatic  cords  or  cords  of 
liver  cells.  There  are  two  views  as  to  the  manner  of  transformation.  The 
older  view  is  that  the  cylinders  gradually  become  stretched,  the  number  of  cells 
in  cross-section  becoming  less  until  it  is  reduced  to  two.  Between  these  two 
lies  the  lumen  of  the  cord  or  the  so-called  "bile  capillary"  (Fig.  315,  B).  The 
other  view  is  that  branches  from  the  sinusoids  grow  into  the  cylinders  and  sub- 
divide them  into  hepatic  cords. 

As  stated  above,  the  hepatic  cylinders  are  at  first  composed  of  darkly  stain- 
ing, polyhedral  cells  with  vesicular  nuclei.  These  are  the  liver  cells  proper. 
Later  other  small  spherical  cells,  with  dense  nuclei,  appear  and  during  the 
fourth  month  become  very  numerous  (Fig.  315,  A).  From  this  time  on,  they 
grow  less  in  number  and  at  birth  have  practically  disappeared.  Earlier  investi- 
gators considered  them  as  developing  liver  cells.  Further  study  on  the  develop- 
ment of  the  blood,  however,  has  led  others  to  consider  them  as  erythroblasts 
(p.  270).  Since  they  are  inside  of  the  hepatic  cylinders,  they  either  wander  in 
from  the  intertrabecular  blood  vessels  or  lie  in  intratrabecular  vessels.  The 
latter  supposition  accords  with  the  view  that  the  cylinders  are  broken  up  into 
hepatic  cords  by  the  ingrowth  of  branches  from  the  sinusoids. 

The  development  of  the  lobules  of  the  liver,  producing  the  peculiar  relations 


350 


TEXT-BOOK  OF  EMBRYOLOGY^ 


between  the  parenchyma  of  the  gland  and  the  blood  vessels,  has  not  been 
clearly  and  completely  demonstrated.  In  young  embryos  the  branches  of  the 
hepatic  veins  are  surrounded  by  comparatively  little  connective  tissue.  The 
branches  of  the  portal  vein  are  surrounded  by  a  considerable  amount  which 
subdivides  the  liver  into  lobules  but  not  in  the  same  manner  as  in  the  adult. 
The  trabeculae  possess  no  radial  character  and  there  are  several  so-called  central 
veins  in  each  lobule.  The  changes  by  which  these  primary  lobules  are  sub- 
divided into  the  permanent  ones  do  not  take  place  until  after  birth.  The 
branches  of  the  portal  vein,  with  the  surrounding  connective  tissue,  invade  the 


A 


FIG.  315. — Sections  of  the  liver  of  (A)  a  human  foetus  of  6  months  and  (B)  a  child  of  4  years. 

Toldt  and  Zuckerhandl.  McMurrich. 
bcs.  Bile  "capillary";  e,  erythroblast;  he,  hepatic  cylinder  (in  A),  cord  of  liver  cells  (in  B). 

primary  lobules  and  divide  them  into  a  number  of  secondary  lobules,  corre- 
sponding to  the  original  number  of  central  veins.  At  the  same  time  the  hepatic 
cords  (which  have  been  formed  meanwhile)  become  arranged  radially  around 
the  central  veins  in  the  characteristic  manner.  The  hepatic  artery  grows  into 
the  liver  secondarily  and  its  branches  follow  the  course  of  the  branches  of  the 
portal  vein. 

Degeneration  of  the  liver  cells  occurs  in  the  region  of  the  left  triangular  liga- 
ment, the  gall  bladder  and  the  inferior  vena  cava.  The  bile  ducts  may,  how- 
ever, withstand  the  degenerative  processes  and  persist  as  the  vasa  aberrantia  of 
the  liver.  The  cause  of  the  degeneration  is  possibly  the  pressure  brought  to 
bear  by  other  organs. 

The  Development  of  the  Pancreas. 

The  epithelium  of  the  pancreas,  like  that  of  the  liver,  is  a  derivative  of  the 
entoderm.  It  arises  from  two  (or  three)  separate  anlagen,  one  dorsal  and  one 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       351 


(or  two)  ventral.  The  dorsal  anlage  appears  first  as  a  ridge-like  evagination 
from  the  dorsal  wall  of  the  gut,  slightly  cranial  to  the  level  of  the  liver  (Figs.  311 
and  312).  It  appears  about  the  same  time  as  the  liver  or  a  little  later.  The 
mass  of  cells  grows  into  the  dorsal  mesentery  and  becomes  constricted  from 
the  parent  epithelium  except  for  a  thin  neck  which  becomes  the  duct  of 
Santorini  (Fig.  316).  A  little  later  two  other  diverticula  appear,  one  from  each 
side  of  the  common  bile  duct.  It  is  uncertain  whether  only  one  or  both  of  these 


Stomach 


Liver 


Cystic  duct 


Dorsal  pancreas  - — 


Gall  bladder 

Ductus  choledochus 
Ventral  pancreas 


Ductus  choledochus 


Liver 


Dorsal  pancreas 

Acces.  pancr.  duct 
(Santorini) 


Duodenum 


Cystic  duct 


Gall  bladder 


Ventral  pancreas  with 
pancr.  duct  (Wirsung) 
FIG.  317. 

FIGS.  316  and  317. — From  models  of  the  developing  liver  and  pancreas  of  rabbit  embryos  of 
8  mm.  and  10  mm  ,  respectively-.     Both  seen  from  the  right  side.     Hammar,  Bonnet. 

take  part  in  the  formation  of  the  pancreas,  but  it  seems  most  probable  that  the 
left  one  disappears  entirely.  The  right  diverticulum  continues  to  develop  and 
becomes  constricted  from  the  parent  epithelium,  leaving  only  a  thin  neck  which 
becomes  the  duct  of  Wirsung. 

The  smaller  ventral  pancreas  grows  to  the  right  and  then  dorsally  in  the 
mesentery  (Fig.  318),  passing  over  the  right  surface  of  the  portal  vein,  until  it 
meets  and  fuses  with  the  proximal  part  of  the  larger  dorsal  pancreas.  The 
fusion  takes  place  in  the  sixth  week,  and  the  two  anlagen  then  form  a  single 


352 


TEXT-BOOK  OF  EMBRYOLOGY. 


mass.  A  communication  is  established  between  the  two  ducts,  and  the  dorsal 
duct  (Santorini)  usually  disappears,  leaving  the  ventral  (Wirsung)  as  the  per- 
manent duct  opening  into  the  ductus  choledochus.  In  a  general  way  it  may  be 
said  that  the  ventral  anlage  gives  rise  to  the  head,  the  dorsal  anlage  to  the  body 
and  tail  of  the  pancreas  (compare  Figs.  316  and  317). 

As  the  pancreas  grows  into  the  dorsal  mesentery  it  comes  to  lie  in  the 
dorsal  mesogastrium  between  the  greater  curvature  of  the  stomach  and  the 
vertebral  column,  and  since  the  dorsal  mesogastrium  at  first  lies  in  the  medial 
sagittal  plane,  the  pancreas  is  similarly  situated.  After  the  sixth  week,  how- 
ever, as  the  stomach  changes  its  position  (p.  335),  the  pancreas  is  carried  along 


Inf.  vena  cava 


Coelom 

Dorsal  pancreas 

Portal  vein 

Ventral  pancreas 

Ductus  choledochus 


Right  side 


Mesonephros 


Greater  omentum 
(dorsal  mesentery) 


Duodenum 


Liver 


L«ft  side 


FIG.  318. — From  a  transverse  section  through  the  region  of  the  duodenum  of  a  pig 
embryo  of  14  mm.     Photograph. 

with  the  mesogastrium  and  comes  to  lie  in  a  transverse  plane,  with  its  head  to 
the  right  and  embedded  in  the  bend  of  the  duodenum,  and  its  tail  reaching  to 
the  spleen  on  the  left.  The  organ  as  a  whole  is  at  first  movable  along  with  the 
mesentery,  but  when  it  assumes  its  transverse  position  it  lies  close  to  the  dorsal 
abdominal  wall.  The  mesentery  then  fuses  with  the  adjacent  peritoneum 
(see  p.  380),  and  the  pancreas  is  firmly  fixed. 

The  connective  tissue  of  the  pancreas  is  derived  from  the  mesodermal  tissue 
of  the  mesentery.  As  the  processes  or  buds  which  form  the  ducts  and  terminal 
tubules  grow  out  from  the  primary  masses,  they  penetrate  the  mesodermal 
tissue  and  are  surrounded  by  it.  Groups  of  tubules  form  lobes  and  lobules, 
and  the  entire  gland  is  surrounded  by  a  capsule  of  connective  tissue. 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.   353 

Histogenesis  of  the  Pancreas. — The  masses  of  entodermal  cells  forming 
the  anlagen  of  the  pancreas  develop  further  by  a  process  of  budding,  which 
goes  on  until  finally  a  compound  tubular  gland  is  produced.  According  to 


FIG.  319. — Sections  of  the  developing  pancreas  of  a  guinea-pig  embryo  of  12  mm.  (a); 

of  33  mm.  (6) ;  of  Torpedo  marmorata  (c) .    Helly. 

c,  Capillaries;  Dg,  ducts;  Gz,  duct  cells;  Lz,  Langhans'   cells.     The  cells  in  c  show- 
distinct  zymogen  granules 

some  investigators  the  primary  evaginations  are  hollow,  their  lumina  being 
continuous  with  the  lumen  of  the  gut.  According  to  others  they  are  solid  at 
first  and  acquire  their  lumina  secondarily.  The  same  uncertainty  exists  in 
regard  to  the  later  outgrowths  or  buds. 


354  TEXT-BOOK  OF  EMBRYOLOGY. 

The  early  entodermal  cells  proliferate,  and  the  resulting  cells  change  ac- 
cording to  their  position  in  the  gland.  Those  lining  the  larger  ducts  become 
high  columnar,  with  more  or  less  homogeneous  cytoplasm;  those  lining  the 
intermediate  (intercalated)  ducts  become  low;  those  lining  the  terminal  secret- 
ing tubules  become  pyramidal  and  more  highly  specialized,  and  also  acquire 
certain  constituents — the  zymogen  granules  (Fig.  319,  c) — which  vary  with  the 
functional  activities  of  the  gland.  The  centro-tubular  cells  in  the  terminal 
tubules  are  probably  to  be  explained  on  a  developmental  basis.  While  a  few 
maintain  that  they  are  "wandering"  cells,  it  is  quite  generally  accepted 
that  they  are  simply  continuations  of  the  flat  cells  lining  the  intermediate 
ducts,  the  result  being  that  the  cells  of  the  terminal  tubules  seem  to 
spread  out  over  the  ends  of  the  intermediate  ducts  in  the  form  of  cap-like 
structures. 

It  was  once  thought  that  the  islands  of  Langerhans  were  derived  from  the 
mesodermal  tissue.  Recently  it  has  been  pretty  clearly  demonstrated  that  they 
are  derived  from  entoderm.  In  guinea-pig  embryos  of  5  to  6  mm.,  at  a  time 
when  the  dorsal  pancreas  has  merely  begun  its  constriction  from  the  gut,  certain 
cells  in  the  mass  appear  darker  and  slightly  larger  than  the  others.  They  show 
darker  areas  of  cytoplasm  around  the  nuclei,  and  later  the  darker  areas  extend 
throughout  the  cells  and  the  nuclei  become  larger  and  more  vesicular.  When 
lumina  appear  in  the  outgrowths  or  buds,  these  cells  occupy  a  position  on  or  near 
the  surface  of  the  buds  (Fig.  319,  a).  In  further  development  they  tend  to  sepa- 
rate themselves  from  the  buds  and  collect  in  clumps  (Fig.  319,  b).  Capillaries 
then  penetrate  the  clumps  and  break  them  up  into  the  trabeculae  of  cells  char- 
acteristic of  the  islands  of  Langerhans  (Fig.  3 1 9,  c) .  Studies  on  the  development 
of  the  islands  in  the  human  pancreas  indicate  a  similar  origin  and  mode  of 
development. 

Anomalies. 

One  of  the  most  striking  anomalies  of  the  organs  of  alimentation  is  found 
in  connection  with  a  more  general  anomalous  condition  known  as  transposition 
of  the  viscera  (situs  viscerum  inversus).  The  transposition  may  be  so  complete 
that  the  minor  asymmetries  normally  present  on  the  two  sides  are  all  repeated 
in  reverse  order,  the  functions  of  the  organs  being  unimpaired.  As  regards  the 
alimentary  tract,  this  means  that  the  position  of  the  stomach  is  reversed  in  the 
abdominal  cavity;  that  the  duodenum  crosses  from  left  to  right;  that  the  various 
coils  of  the  jejunum  and  ileum  occupy  positions  opposite  to  the  normal;  that  the 
caecum  and  ascending  colon  are  situated  on  the  left  side  and  the  descending 
colon  on  the  right;  and  that  the  larger  lobe  of  the  liver  lies  on  the  left  side.  The 
other  visceral  organs  are  transposed  accordingly,  the  heart  being  inclined  to- 
ward the  right  side,  the  left  lung  consisting  of  three  lobes  and  the  right  of  two, 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       355 

the  left  kidney  being  lower  than  the  right,  etc.  Such  cases  are  not  uncommon, 
two  hundred  being  on  record. 

Various  theories  as  to  the  causes  of  transposition  of  the  organs  have  been 
advanced.  In  the  most  plausible  of  these  the  anomalous  condition  is  consid- 
ered as  due  to  the  influence  of  the  large  veins  in  the  embryo.  It  seems  best, 
therefore,  to  consider  first  the  transposition  of  the  heart  (dextrocardia,  referred 
to  on  page  286). 

After  the  two  anlagen  unite  in  the  midventral  line,  the  heart  constitutes  a 
simple  straight  tube  which  lies  in  a  longitudinal  direction  in  the  primitive  peri- 
cardial  cavity,  and  which  is  joined  caudally  by  the  two  omphalomesenteric 
veins  and  cranially  by  the  ventral  aortic  trunk  (p.  228).  Normally  the  left 
omphalomesenteric  vein  is  the  larger  and  pours  a  greater  quantity  of  blood  into 
the  heart  tube  than  the  right.  This  condition  is  regarded  as  the  primary  factor 
in  the  deflection  of  the  tube  toward  the  right  side  (p.  230;  also  Fig.  196).  If  the 
conditions  were  reversed,  that  is,  if  the  right  omphalomesenteric  vein  were  the 
larger  and  poured  the  greater  quantity  of  blood  into  the  heart  tube,  the  pri- 
mary bend  of  the  latter  would  be  toward  the  left  side.  Consequently  the  heart 
would  continue  to  develop  in  the  transposed  position  and  eventually  come  to 
lie  on  the  side  opposite  to  the  normal. 

Although  dextrocardia  is  very  frequently  associated  with  transposition  of 
the  abdominal  organs,  it  is  not  necessarily  so,  for  there  are  cases  of  the  latter  in 
which  the  heart  occupies  the  normal  position.  Consequently  it  seems  that 
further  influences  must  be  present  to  account  for  transposition  of  the  abdominal 
organs  when  the  thoracic  organs  are  normal.  A  number  of  investigators  have 
emphasized  the  importance  of  the  influence  of  the  large  venous  trunks  in  the 
abdominal  region,  especially  on  the  position  of  the  liver  and  stomach. 

Primarily  the  omphalomesenteric  veins  pass  cranially  through  the  mesen- 
tery. Later  they  form  two  loops  or  rings  around  the  duodenum.  Then  the 
left  half  of  the  upper  ring  and  the  right  half  of  the  lower  disappear,  the  common 
venous  trunk  thus  following  a  spiral  course  around  the  duodenum  (p.  262;  also 
Fig.  239).  This  primary  relation  of  the  omphalomesenteric  vein  is  retained  in 
the  relation  of  the  portal  vein  to  the  duodenum.  The  stomach  lies  to  the  left 
of  the  portal  vein.  After  the  allantoic  (placental)  circulation  is  established  the 
umbilical  veins  pass  cranially  in  the  lateral  body  walls.  After  the  veins  come 
into  connection  with  the  liver,  the  right  atrophies  and  the  left  increases  in  size 
and  becomes  the  single  large  umbilical  vein  of  later  stages  (p.  261;  also  Fig.  240). 
The  right  lobe  of  the  liver  becomes  the  larger. 

If,  as  is  maintained  by  some  investigators,  the  usual  position  of  the  stomach 
and  liver  is  due  to  the  persistence  of  the  left  venous  trunks,  a  persistence  of  the 
right  venous  trunks  would  afford  a  plausible  explanation  of  the  transposition  of 
these  organs.  It  is  not  unreasonable  to  attribute  also  the  transposition  of  the 


356  TEXT-BOOK  OF  EMBRYOLOGY. 

other  abdominal  organs  directly  or  indirectly  to  the  persistence  of  the  right 
venous  trunks.  Certainly  a  reversal  in  the  position  of  the  stomach  would 
cause  a  reversal  in  the  position  of  the  duodenum. 

If  these  conditions  are  the  real  ones,  the  fact  that  the  thoracic  organs  can  be 
transposed  without  a  transposition  of  the  abdominal  organs,  or  vice  versa, 
is  accounted  for.  The  primary  bend  of  the  heart  tube  occurs  at  a  very  early 
period,  before  the  changes  in  the  vessels  in  the  region  of  the  liver.  Conse- 
quently a  reversal  of  the  conditions  of  the  omphalomesenteric  at  a  very  early 
stage  only  would  be  likely  to  affect  the  heart.  The  principal  changes  in  size 
of  the  venous  trunks  in  the  abdominal  region  take  place  after  their  channels 
have  been  broken  up  in  the  liver.  In  other  words,  the  modifications  in  the  veins 
in  the  liver  occur  after  the  definite  relations  of  the  heart  have  been  established. 
Therefore  the  transposition  of  the  abdominal  organs  may  take  place  after  the 
heart  has  begun  to  develop  normally. 

THE  MOUTH. — Anomalies  in  the  mouth  region,  due  to  defective  fusion  of 
the  processes  that  bound  it,  have  been  considered  elsewhere  (p.  212). 

Anomalies  of  the  tongue  sometimes  arise  as  the  result  of  imperfect  develop- 
ment of  one  or  more  of  its  anlagen.  Imperfect  development  of  the  tuberculum 
impar  results  in  total  or  partial  lack  of  the  anterior  part.  Defects  in  the  root 
are  probably  due  to  imperfect  development  of  one  or  both  of  the  paired  anlagen 
(p.  320).  Malformations  of  the  lower  jaw  (micrognathus,  agnathus)  are 
usually  accompanied  by  malformations  of  the  tongue,  both  structures  being 
derived  largely  from  the  first  pair  of  branchial  arches. 

THE  PHARYNX. — The  pharynx  is  the  seat  of  cysts,  fistulae  and  diverticula 
which  have  been  considered  in  connection  with  the  anomalies  in  the  region  of 
the  branchial  arches  and  grooves  (Chap.  XIX) . 

The  ihyreoid  gland  is  not  infrequently  the  seat  of  certain  anomalies  that 
arise  as  the  result  of  abnormal  development.  Persistent  portions  of  the  thyreo- 
glossal  duct,  the  upper  end  of  which  is  indicated  by  the  foramen  cascum  linguae, 
may  give  rise  to  cystic  structures  extending  to  the  region  of  the  hyoid  bone. 
Persistent  portions  of  the  duct  may  even  give  rise  to  accessory  thyreoid  (supra- 
hyoid,  prehyoid)  glands  (p.  332;  also  Fig.  298).  Considerable  variation  also 
exists  in  the  isthmus  and  lateral  lobes  of  the  thyreoid,  due  to  variation  in  the 
manner  of  development  of  the  medial  anlage. 

Impaired  development  of  the  thymus  gland  sometimes  leads  to  cysts  which 
come  to  lie  in  the  anterior  mediastinum. 

THE  (ESOPHAGUS. — Very  rarely  the  oesophagus  is  entirely  lacking,  being 
represented  by  a  mere  cord  of  tissue.  More  frequently  it  is  defective  in  certain 
parts.  The  atresia  may  begin  just  below  the  pharynx  or  just  above  the  stomach, 
the  intermediate  portion  being  composed  of  a  cord  of  fibrous  tissue.  Occasion- 
ally the  non-atretic  portion  opens  into  the  trachea.  Possibly  this  represents 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.       357 

an  imperfect  separation  between  the  primitive  gut  and  the  anlage  of  the 
respiratory  system  (p.  360). 

THE  STOMACH. — Occasionally  the  stomach  is  smaller  than  the  normal.  It 
may  even  be  a  narrow  tube  resembling  the  other  portions  of  the  gut,  owing  to 
lack  of  dilatation.  Other  congenital  malformations,  apart  from  transposition 
(p.  354),  are  very  rare. 

THE  INTESTINES. — One  of  the  most  common  anomalies  is  the  persistence  of 
the  proximal  end  of  the  yolk  stalk,  forming  Meckel's  diverticulum  (see  p.  113). 
This  usually  is  attached  to  the  ileum  about  three  feet  from  the  caecum.  In  ex- 
ceptional cases  it  retains  its  lumen  and,  when  the  stump  of  the  umbilical  cord 
disappears,  forms  a  congenital  umbilical  fistula.  Usually,  however,  the  diver- 
ticulum  is  shorter  and  ends  blindly.  Occasionally  it  becomes  constricted  from 
the  intestine  and  forms  a  cystic  structure.  (See  also  Chap.  XIX.) 

Congenital  stenosis  and  atresia  may  occur  in  different  regions  of  the  intestine, 
the  duodenum  being  the  most  common  site.  Normally  the  lumen  of  the 
duodenum  becomes  closed  for  a  brief  period  during  development  (p.  338),  and 
congenital  closure  of  the  lumen  may  represent  a  persistence  of  the  early  em- 
bryonic condition. 

A  conspicuous  malformation  is  the  persistence  of  the  cloaca.  The  septum 
which  normally  separates  the  latter  structure  into  rectum  and  urogenital  sinus 
fails  to  develop,  thus  leaving  a  common  cavity  (see  Figs.  361  and  362).  In 
addition  to  this  the  cloacal  membrane  may  fail  to  rupture  and  the  cloaca  be- 
come much  distended.  More  often  the  septum  develops  in  part,  leaving  only 
a  small  opening  between  the  rectum  and  urogenital  sinus.  After  the  latter 
undergoes  further  development,  the  rectum  comes  to  open  into  the  urethra  or 
bladder,  or  into  the  vagina  or  uterus. 

Atresia  of  the  anus  is  not  infrequently  met  with.  The  cloacal  (or  anal) 
membrane  fails  to  rupture  and  the  rectum  ends  blindly.  In  other  cases  the 
rectum  opens  into  the  urogenital  sinus,  as  described  in  the  preceding  paragraph. 
Occasionally  the  lumen  of  the  rectum  is  closed — atresia  recti — and  the  gut  ends 
blindly  some  distance  from  the  surface,  being  connected  with  the  anal  region  by 
a  cord  of  fibrous  tissue. 

Variations  in  the  position  of  the  intestinal  loops,  apart  from  transposition  (p. 
?54^,  are  of  frequent  occurrence.  It  is  not  customary  to  include  these  varia- 
tions among  malformations  (see  p.  339).  The  caecum  (and  appendix)  and  colon 
present  some  striking  variations.  The  caecum  may  be  situated  high  up  in  the 
abdominal  cavity,  the  ascending  colon  being  absent.  Or  it  may  be  situated  at 
any  intermediate  point  between  that  and  its  usual  position  in  the  right  iliac 
fossa.  These  variations  are  due  to  different  degrees  of  development  of  the 
ascending  colon  (p.  340). 

THE  LIVER. — Congenital  malformations  of  the  liver  are  rare.     The  most 


358  TEXT-BOOK  OF  EMBRYOLOGY. 

frequent,  apart  from  transposition,  include  anomalies  in  the  size  and  number  of 
lobes.  Accessory  lobes  may  occur  within  the  falciform  ligament.  One  case 
of  lack  of  development  of  the  gall  bladder  has  been  observed.  Stenosis  of  the 
bile  passages  is  occasionally  met  with. 

THE  PANCREAS. — Occasionally  accessory  glands  are  found  in  the  intesti- 
nal or  gastric  wall.  These  probably  represent  aberrant  portions  of  the  main 
gland,  and  may  give  rise  to  cystic  structures.  Very  recently,  however,  a 
number  of  intestinal  diverticula  have  been  observed  in  certain  mammalian 
embryos  and  also  in  human  embryos.  Although  the  history  of  these  unusual 
diverticula  has  not  been  traced,  their  presence  may  offer  a  clue  to  the  origin  of 
accessory  pancreatic  structures.  The  ducts  of  the  pancreas  are  subject  to 
distinct  variations,  which,  however,  are  not  usually  considered  as  anomalies. 
Not  infrequently  the  duct  of  the  dorsal  anlage  (duct  of  Santorini)  persists  and 
opens  directly  into  the  duodenum.  It  may  persist  along  with  the  duct  of  the 
ventral  anlage  (duct  of  Wirsung),  or  the  latter  may  disappear  (p.  352;  compare 
Figs.  316  and  317). 

References  for  Further  Study. 

BELL,  E.  T.:  The  Development  of  the  Thymus.     American  Jour,  of  Anat.,  Vol.  V,  1906 

BERRY,  J.  M.:  On  the  Development  of  the  Villi  of  the  Human  Intestine.  Anat.  Anz. 
Bd.  XVI,  1900. 

BONNET,  R.:  Lehrbuch  der  Entwickelungsgeschichte.    Berlin,  1907. 

BORN,  G.:  Ueber  die  Derivate  der  embryonalen  Schlundbogen  und  Schlundspalten  bei 
Saugetiere.  Arch.  f.  mik.  Anat.,  Bd.  XXII,  1883. 

BRACHET,  A.:  Die  Entwickelung  und  Histogenese  der  Leber  und  des  Pancreas.  Ergeb- 
nisse  der  Anat.  u.  Entwick.,  Bd.  VI,  1897. 

CHIEVITZ,  J.  C.:  Beitrage  zur  Entwickelungsgeschichte  der  Speicheldrusen.  Arch.  /. 
Anat.  u.  PhysioL,  Anat.  Abth.,  1885. 

CHORONSCHITZKY:  Die  Entstehung  der  Milz,  Leber,  Gallenblase,  Bauchspeicheldruse 
und  des  Pfortadersystems  bei  den  verschiedenen  Abteilungen  der  Wirbeltiere.  Anat.  Hefte, 
Bd.  XIII,  1900. 

Fox,  H.:  The  Pharyngeal  Pouches  and  their  Derivatives  in  the  Mammalia.  Am.  Jour. 
of  Anat.,  Vol.  VIII,  No.  3,  1908. 

FUSARI,  R.:  Sur  les  phenomenes,  que  Ton  observe  dans  la  muqueuse  du  canal  digestif 
durant  le  developpement  du  foetus  humain.  Arch.  ital.  BioL,  T.  XLII,  1904. 

GOPPERT,  E.:  Die  Entwickelung  des  Mundes  und  der  Mundhohle  mit  Driisen  und 
Zunge;  die  Entwickelung  der  Schwimmblase,  der  Lunge  und  des  Kehlkopfes  der  Wirbeltiere. 
In  Hertwig's  Handbwh  der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere.  Bd. 
II,  Teil  I,  1902. 

HAMMAR,  J.  A.:  Einige  Plattenmodelle  zur  Beleuchtung  der  friiheren  embryonalen 
Leberentwickelung.  Arch.  /.  Anat.  u.  PhysioL,  Anat.  Abth.,  1893. 

HAMMAR,  J.  A.:  Allgemeine  Morphologic  der  Schlundspalten  beim  Menschen.  Entwick- 
elung des  Mittelohrraumes  und  des  ausseren  Gehorganges.  Arch.  /.  mik.  Anat.,  Bd.  LIX, 
1902. 

HAMMAR,  J.  A.:  Das  Schicksal  der  zweiten  Schlundspalte.     Zur  vergleichenden  Env 


DEVELOPMENT  OF  THE  ALIMENTARY  TUBE  AND  APPENDED  ORGANS.   359 

bryologie  und  Morphologic  der  Tonsille.     Arch.  /.  mik.  Anat.,  Bd.  LXI,  1903. 

HELLY,  K.:  Studien  iiber  Langerhanssche  Inseln.  Arch.  f.  mik.  Anat.,  Bd.  LXVII, 
1907. 

HERTWIG,  O. :  Lehrbuch  der  Entwickelungsgeschichte  der  Wirbeltiere  und  des  Menschen. 
Jena,  1906. 

HEXDRICKSOX,  W.  F.:  The  Development  of  the  Bile  Capillaries  as  Revealed  by  Golgi's 
Method.  Johns  Hopkins  Hasp.  Bull.,  1898. 

His,  W.:  Anatomic  menschlicher  Embryonen.     Leipzig,  1880-1885. 

His,  W.:  Die  Entwickelung  der  menschlichen  und  tierischen  Physiognomien.  Arch.  f. 
Anat.  u.  Physiol.,  Anat.  Abth.,  1892. 

KOHN,  A.:  Die  Epithelkorperchen.    Ergebnisse  der  Anat.  u.  Enluick.,  Bd.  IX,  1899. 

KOLLMANN,  J.:  Die  Entwickelung  der  Lymphknotchen  in  dem  Blinddarm  und  in  dem 
Processus  vermiformis.  Die  Entwickelung  der  Tonsillen  und  die  Entwickelung  der  Milz. 
Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1900. 

KOLLMAXX,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1907. 

MALL,  F.  P.:  Ueber  die  Entwickelung  des  menschlichen  Darmes  und  seiner  Lage  beim 
Erwachsenen.  Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.  Suppl.,  1897. 

MAURER,  F.:  Die  Entwickelung  des  Darmsystems.  In  Hertwig's  Handbuch  der  ver- 
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PEARCE,  R.  M.:  The  Development  of  the  Islands  of  Langerhans  in  the  Human  Embryo. 
American  Jour,  of  Anat.,  Vol.  II,  1903. 

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Bd.  XXXVIII,  1891. 

STEIDA,  A.:  Ueber  Atresia  ani  congenita  und  die  damit  verbundenen  Missbildungen. 
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STOHR,  P.:  Ueber  die  Entwickelung  der  Darmlymphknotchen  und  iiber  die  Riickbildung 
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1897. 


CHAPTER  XIII. 
THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM. 

The  anlage  of  the  respiratory  system  appears  in  human  embryos  of  about 
3.2  mm.  A  hollow,  linear  evagination — the  lung  groove — develops  on  the 
ventral  side  of  the  cesophageal  portion  of  the  primitive  gut,  extending  caudally 
a  short  distance  from  the  region  of  the  fourth  inner  branchial  groove.  It  was 
once  thought  that  the  evagination  developed  along  practically  the  entire  length 
of  the  oesophagus  anlage,  but  more  recent  researches  seem  to  prove  that  it  is 
confined  to  the  cephalic  end.  The  lung  groove  soon  becomes  separated  from 


Pharynx 


Hypophysis 


Branchial  arches 
(pharynx) 


Lung 

Liver 

Stomach 

Pancreas 

Common 
mesentery 

Mesonephros 
Allantoic  duct 


Hind-gut 

^^  \^^^  w 

Kidney  bud 
FIG.  320. — Sagittal  section  of  reconstruction  of  a  human  embryo  of  5  mm.     His,  Kollmann. 

the  gut  by  a  constriction  which  appears  at  the  caudal  end  and  gradually  pro- 
gresses forward.  Thus  there  is  formed  a  tube  which  lies  ventral  to  the  gut  and 
which  opens  upon  the  floor  of  the  latter  at  the  boundary  line  between  the 
oesophagus  and  pharynx  (Figs.  320  and  284). 

From  this  simple  tube  the  entire  respiratory  system  develops.  The 
cephalic  end  gives  rise  to  the  larynx,  the  opening  into  the  gut  being  the  aditus 
laryngis.  The  middle  portion  gives  rise  to  the  trachea.  Two  outgrowths  from 
the  caudal  end  of  the  tube,  which  appear  about  the  time  of  separation  from  the 

360 


THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM.  361 

oesophagus,  develop  into  the  bronchi  and  their  continuations — the  lungs.  The 
epithelial  lining  of  the  system  is  of  course  derived  from  the  entoderm.  The 
various  kinds  of  connective  tissue  are  derived  from  the  mesoderm,  since  the 
anlage  grows  into  the  mesodermal  tissue  of  the  ventral  mesentery. 

The  Larynx. 

The  opening  from  the  gut  into  the  respiratory  tube  becomes  surrounded  by 
a  U-shaped  elevation — thefurcula — which  lies  in  the  floor  of  the  pharynx  with 
its  open  end  directed  caudally.  Toward  the  end  of  the  first  month  each 
side  of  the  opening  (aditus  laryngis)  becomes  elevated,  forming  the  arytenoid 
ridge.  From  each  of  these  a  secondary  elevation  arises,  forming  the  cunei- 
form ridge.  The  arytenoid  ridges  come  so  close  together  that  they  practically 
close  the  opening  except  at  its  cephalic  side  (Fig.  321).  Along  with  the  develop- 
ment of  these  ridges  the  apical  portion  of  the  furcula  becomes  a  distinct  trans- 


Tuberculum  impar 
i 


^B-  Epiglottis 
^^^^^-  Aryepiglottic  ridge 

-' 

/    &JT~ Arytenoid  ridge 

--/•  — I Cuneiform  ridge 

— j —  Aditus  laryngis 

-__^_^_—  Cuneiform  ridge 


A 


FIG.  321. — From  a  reconstruction  of  the  larynx  of  a  human  embryo  of  28  days. 
Seen  from  above.     Kallius. 

verse  fold  at  the  cephalic  rim  of  the  opening.  This  fold  is  the  anlage  of  the 
epiglottis.  Laterally  the  epiglottic  fold  becomes  continuous  with  the  arytenoid 
ridges,  forming  the  aryepiglottic  ridges  (Fig.  321). 

During  the  fourth  month  a  groove-like  depression  appears  on  the  medial 
side  of  each  arytenoid  ridge,  gradually  becomes  deeper,  and  leaves  on  each  side 
of  it  a  fold  or  lip  which  bounds  the  opening.  The  external  lips — those  nearer 
the  pharynx — form  the  superior  or  false  vocal  cords;  the  internal  lips  form  the 
true  vocal  cords.  At  the  same  time  the  opening  into  the  larynx,  which  was 
closed  by  the  arytenoid  ridges,  is  reestablished.  The  depression  between  the 
vocal  cords  on  each  side  becomes  still  deeper  to  form  the  ventricle,  and  a  further 
outgrowth  from  the  ventricle  produces  the  appendage  of  the  ventricle  (the  laryn- 
geal  pouch). 


362 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  mesodermal  tissue  external  to  the  epithelium  (entoderm)  of  the  larynx 
gives  rise  to  the  various  kinds  of  connective  tissue  including  the  laryngeal 
cartilages.  By  the  end  of  the  fourth  week  condensations  appear  in  the  mesen- 
chymal  tissue,  which  are  the  forerunners  of  the  cartilages,  but  true  cartilage 
does  not  appear  until  the  seventh  week.  The  anlagen  of  the  thyreoid  cartilage 

Sup.  hy. 


Inf.  hy. 


Thyr. 


FIG.  322. — From  reconstructions  of  the  mesenchymal  condensations  which  represent  the  hyoid  and 
thyreoid  cartilages  in  an  embryo  of  40  days.  A,  Ventral  view;  B,  lateral  view  from  right. 
Kallius. 

Inf.hy.,  Inferior  (greater)  horn  of  hyoid;  Sup.hy.,  superior  (lesser)  horn  of  hyoid;  Thyr.,  thyreoid. 
The  portions  indicated  by  black  lines  represent  chondrification  centers. 

are  two  mesenchymal  plates,  one  on  each  side,  which  are  bilaterally  sym- 
metrical and  correspond  to  the  lateral  parts  of  the  adult  cartilage  (Fig.  322,  A). 
These  plates  gradually  grow  ventrally  and  unite  and  fuse  in  the  midventral 
line  (Fig.  323).  Two  centers  of  chondrification  appear  in  each  plate  (Fig.  322, 4,) 

Pharynx 

.       /  Muscle 

"'      ••'•.-.  Arytenoid  cartilage 


i—  Thyreoid  cartilage 


Muscle 


Copula 


FIG.  323. — From  a  transverse  section  through  the  pharynx  and  larynx  of  a  human 
embryo  of  48  mm.     Nicolas. 

and  enlarge  until  the  entire  plate  is  converted  into  cartilage,  the  middle  part 
becoming  elastic  in  character,  the  rest  hyalin. 

Originally  the  cephalic  edge  of  each  thyreoid  plate  is  connected  with  the 
inferior  horn  of  the  hyoid  cartilage  (Fig.  322,  B).  This  connection  is  subse- 
quently lost,  but  a  remnant  of  the  connecting  cartilage  persists  as  the  triticeous 


THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM.  363 

cartilage  in  the  lateral  hyothyreoid  ligament.  The  anlagen  of  the  arytenoid 
cartilages  develop  in  the  arytenoid  ridges  as  condensations  of  the  mesenchyme, 
which  later  are  converted  into  true  cartilage  (Fig.  323).  The  apex  and  vocal 
process  of  each  arytenoid  become  elastic,  the  main  body  becomes  hyalin. 
The  corniculate  cartilages  (cartilages  of  Santorini)  are  split  off  from  the  cephalic 
ends  of  the  arytenoids  and  are  of  the  elastic  variety.  The  cricoid  cartilage, 
like  the  others,  is  preceded  by  a  condensation  of  mesenchyme.  Chondrifica- 
tion  begins  on  each  side  and  then  progresses  around  dorsally  and  ventrally  until 
a  complete  hyalin  ring  is  formed.  From  its  developmental  resemblance  to  the 
tracheal  rings,  the  cricoid  is  sometimes  regarded  as  the  most  cephalic  of  that 
series.  The  epiglottic  cartilage  develops  in  the  epiglottic  ridge  as  two  sepa- 
rate pieces  which  subsequently  fuse.  It  is  of  the  elastic  variety.  The  cuneiform 
cartilages  (cartilages  of  Wrisberg)  are  split  off  from  the  two  pieces  of  the  epi- 
glottic, and  are  of  the  elastic  type. 

Attempts  have  been  made  to  determine  which  branchial  arches  are  represented  by  the 
laryngeal  cartilages.  It  seems  quite  definitely  settled  that  the  thyreoid  is  derived  in  part,  at 
least,  from  the  fourth  arch.  There  is  much  doubt  as  regards  the  others,  for  there  is  great 
difficulty  in  determining  their  derivation  in  the  human  embryo,  since  the  arches  disappear 
at  such  an  early  stage.  Furthermore,  some  of  these  cartilages  may  represent  arches  which 
are  present  in  lower  forms  but  do  not  appear  in  the  higher  Mammals. 

The  larynx  is  situated  much  farther  cranially  in  the  foetus  and  in  the  new- 
born child  than  in  the  adult.  In  a  five  months  foetus  it  extends  into  the  naso- 
pharyngeal  cavity,  whence  it  migrates  caudally  to  its  adult  position.  The 
laryngeal  skeleton  becomes  ossified  during  postnatal  life.  Ossification  begins 
in  the  thyreoid  and  cricoid  cartilages  at  the  age  of  eighteen  to  twenty  years, 
and  in  the  arytenoids  a  few  years  later.  Three  centers  appear  in  the  thyreoid 
— one  on  each  side  near  the  inferior  cornu  and  one  in  the  medial  line  between 
the  two  wings.  In  the  cricoid,  ossification  begins  near  the  upper  border  on 
each  side,  in  the  arytenoids  at  the  lower  borders.  Ossification  usually  begins 
earlier  and  proceeds  more  rapidly  in  the  male  than  in  the  female. 

As  an  example  of  the  explanation  which  Embryology  offers  of  certain  peculiarities  of 
structure  in  the  adult,  the  case  of  the  recurrent  laryngeal  nerve  may  be  cited.  The  heart  and 
aortic  arches  are  primarily  situated  in  the  cervical  region.  At  that  time  a  branch  of  the 
vagus  on  each  side,  passes  behind  the  fourth  aortic  arch  to  reach  the  larynx.  As  the 
heart  and  arches  recede  into  the  thorax,  the  nerve  is  pulled  caudally  between  its  origin  and 
termination,  so  that  in  the  adult  the  left  nerve  bends  around  the  arch  of  the  aorta  and  the 
right  around  the  subclavian  artery. 

The  Trachea. 

The  portion  of  the  original  tube  between  the  larynx  and  the  two  caudal  out- 
growths which  form  the  bronchi  and  lungs,  develops  into  the  trachea.  It  lies 
ventral  to  the  oesophagus  and  is  surrounded  by  mesodermal  tissue  which  is 


364 


TEXT-BOOK  OF  EMBRYOLOGY. 


destined  to  give  rise  to  the  connective  tissue,  includng  the  cartilage,  of  the  adult 
trachea  (Figs.  284  and  320).  The  development  of  the  tracheal  rings  is  very 
similar  to  that  of  the  laryngeal  cartilages.  During  the  eighth  or  ninth  week  con- 
densations appear  in  the  mesenchyme,  which  are  later  transformed  into  hyalin 
cartilage.  The  rings  are  not  complete  but  remain  open  on  the  dorsal  side.  At 
birth  the  trachea  is  collapsed,  the  ventral  side  being  concave  and  the  dorsal  ends 
of  each  ring  being  in  contact.  After  respiration  begins  it  is  dilated  and  becomes 
more  or  less  rigid.  Ossification  of  the  tracheal  rings  begins  in  the  male  at  the 
age  of  about  forty  years,  in  the  female  at  about  sixty.  The  glands  of  the 
trachea  represent  e vagina tions  from  the  epithelial  linings. 

The  Lungs. 

As  has  been  stated  (p.  360),  the  caudal  end  of  the  original  tube  evaginates 
to  form  two  hollow  buds  which  are  the  beginnings  of  the  two  lungs  (Fig.  324). 
The  evagination  takes  place  soon  after  or  even  along  with  the  separation  of  the 
lung  groove  from  the  gut.  The  right  bud  soon  gives  rise  to  three  secondary 


Aorta 

Upper  limb  bud 

(Esophagus 

Body  cavity 
Pericardial  cavity 


FIG.  324. — Transverse  section  of  a  14  mm.  pig  embryo,  at  the  level  of  the  upper  limb  buds, 
showing  especially  the  two  bronchi. 


buds,  the  forerunners  of  the  three  lobes  of  the  right  lung.  The  left  bud  gives 
rise  to  two  secondary  buds,  the  forerunners  of  the  two  lobes  of  the  left  lung 
(Fig.  325).  The  primary  buds  may  be  said  to  represent  the  two  bronchi  arising 
from  the  trachea,  the  five  secondary  buds  to  represent  the  bronchial  rami 
which  extend  into  the  five  lobes  of  the  lungs.  Successive  evaginations  from 
each  of  the  five  buds  take  place  and  form  an  extensive  arborization  for  each 
lobe  (Figs.  326  and  327). 


THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM. 


365 


The  manner  in  which  the  bronchial  rami  branch  is  not  definitely  known. 
Some  maintain  that  the  branching  is  dichotomous,  that  is,  each  bud  gives  rise 
to  two  equal  buds  and  each  of  these  to  two  others,  and  so  on.  In  order  to  as- 
sume the  adult  form,  however,  one  of  the  buds  places  itself  in  line  with  the 
preceding  bud  or  bronchus  while  the  other  places  itself  as  a  lateral  outgrowth. 
Others  hold  that  the  growth  is  monopodial,  that  is,  that  the  original  bud  grows 
in  a  more  or  less  direct  line  and  the  others  develop  as  lateral  outgrowths.  When 


Upper  right  lobe 
Middle  right  lobe 


Trachea 
Upper  left  lobe 


Mesoderm 
(mesenchyme) 


Lower  right  lobe 

FIG.  325. — Anlage  of  lungs  of  a  human  embryo  of  4.3  mm. 


His. 


the  evaginations  that  produce  the  bronchial  rami  are  completed,  each  terminal 
(respiratory)  bronchus  subdivides  into  three  to  six  narrow  tubules,  the  alveolar 
ducts.  The  latter  again  branch  into  several  wider  compartments,  the  atria, 
from  which  several  air  sacs  are  given  off.  The  walls  of  the  air  sacs  are  evagi- 
nated  to  form  many  closely  set  air  cells  which  represent  the  ultimate  branches 
of  the  air  passages  of  the  lungs. 


Trachea 


Right  bronchus 


Left  bronchus 


Bronchial  ramus 

Mesoderm 
(mesenchyme) 
Bronchial  ramus' 

FIG.  326. — Anlage  of  lungs  of  a  human  embryo  of  8.5  mm.     His. 

While  there  is  a  general  tendency  toward  bilateral  symmetry  in  the  various 
sets  of  bronchial  rami,  the  lobes  of  the  lungs  are  asymmetrical.  This  asym- 
metry is  indicated  in  the  five  secondary  buds  that  arise  from  the  two  primary, 
since  three  arise  on  the  right  side  and  only  two  on  the  left.  The  three  on  the 
right  represent  the  upper,  middle  and  lower  lobes  of  the  right  lung  (Fig.  325). 
The  upper  is  known  as  the  eparterial  from  the  fact  that  its  bronchus  lies  dorsal 


366 


TEXT-BOOK  OF  EMBRYOLOGY. 


to  the  pulmonary  artery.  No  lobe  develops  on  the  left  side  corresponding  to 
the  upper  (eparterial)  on  the  right.  There  is  a  possibility  that  it  is  absent  in 
order  to  allow  the  arch  of  the  aorta  to  migrate  caudally  as  it  normally  does 
(see  p.  254).  One  of  the  larger  ventral  bronchial  rami  of  the  left  lung  is  ab- 
sent, owing  to  the  inclination  of  the  heart  toward  the  left  side;  but  as  a  compensa- 
tion the  corresponding  ramus  of  the  right  lung  develops  more  extensively 
and  projects  into  the  space  between  the  pericardium  and  diaphragm  as  the 
infracardiac  ramus. 

From  the  fact  that  the  anlage  of  the  respiratory  system  is  enclosed  within 
the  mesentery  between  the  gut  and  the  pericardial  cavity,  and  that  its  caudal  end 
becomes  enclosed  within  the  dorsal  edge  of  the  septum  transversum,  it  is  obvious 


Pulmonary  artery 


Right  bronchu 


Upper  right 
bronch.  ramus 


Middle  right 
bronch.  ramus 


Lower  right 
bronch.  ramus 

Mesoderm 
(mesenchyme) 


Trachea 


Left  bronchus 


Upper  left 
bronch.  ramus 

Lower  left  branch 
pulmonary  vein 


Lower  left 
bronch.  ramus 


FIG.  327. — Anlage  of  lungs  of  a  human  embryo  of  10.5  mm.     His, 


that  the  lungs  will  push  their  way  into  the  dorsal  parietal  recesses  or  pleural 
cavities  (Figs.  328  and  333).  The  way  in  which  the  lungs  and  pleural  cavities 
enlarge  and  separate  the  pericardium  from  the  body  wall  on  each  side  and  from 
the  diaphragm  is  described  on  page  376  (see  Figs.  334  and  335).  The  mesoder- 
mal  tissue  that  surrounds  the  primary  lung  buds  is  in  part  pushed  before  the 
numerous  outgrowths  and  in  part  remains  among  them  (Figs.  325,  326,  327). 
The  part  around  the  lungs,  with  its  covering  of  mesothelium,  comes  to  form  the 
visceral  layer  of  the  pleura  which  closely  invests  the  entire  surface  of  the  lungs 
and  dips  down  between  the  lobes.  At  the  roots  of  the  lungs  it  is  continuous 
with  the  parietal  layer  of  the  pleura  lining  the  inner  surface  of  the  pleural  cavi- 
ties. The  mesodermal  tissue  among  the  bronchi  and  their  terminations  gives 
rise  to  the  connective  tissue  that  separates  the  lobes  and  lobules  and  invests  all 
the  structures  in  the  interior  of  the  lungs.  This  connective  tissue  at  first  con- 


THE   DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM. 


367 


stitutes  a  large  part  of  the  lungs,  but  as  development  proceeds,  the  more 
rapid  growth  of  the  respiratory  parts  results  in  the  relatively  small  amount  of 
connective  tissue  characteristic  of  the  adult  lung. 

Changes  in  the  Lungs  at  Birth. — At  birth  the  lungs  undergo  rapid  and 
remarkable  changes  in  consequence  of  their  assuming  the  respiratory  function. 
These  changes  affect  their  size,  form,  position,  texture,  weight,  etc.,  and 
furnish  probably  the  only  certain  means  of  distinguishing  between  a  still-born 
child  and  one  that  has  breathed.  In  the  foetus  at  term  the  lungs  are  small, 
possess  rather  sharp  margins  and  lie  in  the  dorsal  part  of  the  pleural  cavities. 


Diaphragm 


Lungs 


Pleural  ca vities 


FIG.  328. — Transverse  section  of  a  pig  embryo  of  35  mm.,  showing  the  developing  lungs  (bronchial 
rami  surrounded  by  mesoderm).  The  oesophagus  is  seen  between  the  two  lungs;  above  the 
oesophagus  is  the  aorta.  The  dark  mass  in  the  lower  part  of  the  figure  is  the  liver. 
Photograph. 

After  respiration  they  enlarge,  fill  practically  the  entire  pleural  cavities  and 
naturally  become  more  rounded  at  their  margins.  The  introduction  of  air  into 
the  air  passages  converts  the  compact,  gland-like,  fcetal  lung  into  a  loose, 
spongy  tissue.  The  specific  gravity  is  changed  from  1.056  to  0.342.  While 
there  is  a  gradual  increase  in  the  weight  of  the  lungs  during  development,  there 
is  a  very  sudden  increase  at  birth  when  the  blood  is  freely  admitted  to  them 
through  the  pulmonary  arteries.  The  weight  of  the  lungs  relative  to  that  of 
the  body  changes  from  about  i  to  70  before  birth,  to  about  i  to  35  or  40  after 
birth. 


368  TEXT-BOOK  OF  EMBRYOLOGY. 

Anomalies. 

THE  LARYNX. — The  larynx  may  be  excessively  large  or  unusually  small. 
Occasionally  the  epiglottic  cartilage  consists  of  two  pieces,  indicating  a  failure 
of  the  two  anlagen  to  fuse  (p.  362).  Similar  defects  may  occur  in  the  other 
cartilages  that  are  derived  from  more  than  one  anlage.  The  ventricle  on  either 
side  may  be  abnormally  large  with  an  exaggerated  appendage  (laryngeal 
pouch) .  This  condition  resembles  that  in  the  anthropoid  apes. 

THE  TRACHEA. — The  trachea  is  sometimes  absent,  in  which  case  the  bronchi 
arise  immediately  below  the  larynx,  indicating  a  failure  on  the  part  of  the 
original  tube  to  elongate.  The  trachea  may  be  abnormally  short.  Rarely 
there  is  a  direct  communication  between  the  trachea  and  oesophagus,  probably 
due  to  an  incomplete  separation  of  the  lung  groove  from  the  gut  (p.  360).  The 
cartilaginous  rings  may  vary  in  number  as  a  result  of  abnormal  splittings  and 
fusions. 

THE  LUNGS. — Rarely  the  eparterial  bronchial  ramus  on  the  right  side 
arises  as  a  branch  of  the  trachea  and  not  as  a  branch  of  the  bronchus  (p.  365). 
This  condition  is  normal  in  certain  Mammals  (ox,  sheep) .  Rarely  an  eparterial 
bronchial  ramus  is  present  on  the  left  side,  thus  producing  a  third  lobe  for 
the  left  lung.  In  some  animals  an  eparterial  ramus  is  normally  present  on 
each  side,  the  larger  bronchial  rami  thus  being  bilaterally  symmetrical.  Varia- 
tion in  size  and  number  of  lobes  is  not  infrequent.  Supernumerary  or  acces- 
sory lobes,  formed  either  by  evaginations  from  the  original  anlage  or  by  in- 
dependent evaginations  from  the  gut,  are  met  with  in  rare  cases. 

Occasionally  some  portion  of  either  lung  is  defective.  The  bronchial  bud 
that  would  normally  give  rise  to  the  lung  tissue  in  that  region  fails  to  develop 
properly,  and  the  result  is  a  number  of  rami,  without  the  ultimate  terminations, 
surrounded  by  vascular  tissue.  The  rami  may  remain  normal  or  may  become 
dilated  and  form  large  bronchial  cysts. 

References  for  Further  Study. 

BONNET,  R.:  Lehrbuch  der  Entwickelungsgeschichte.  Berlin,  1907. 

FLINT,  J.  M.:  The  Development  of  the  Lungs.    American  Jour,  of  Anat.,  Vol.  VI,  1906. 

GOPPERT,  E.:  Die  Entwickelung  des  Mundes  und  der  Mundhohle  mit  Driisen  irtid 
Zunge;  die  Entwickelung  der  Schwimmblase,  der  Lunge  und  des  Kehlkopfes  der  Wirbeltiere. 
In  Hertwig's  Handbuch  der  vergleich.  u.  experiment.  Entivickelungslehre  der  Wirbeltiere, 
Bd.  II,  Teil  I,  1902. 

HERTWIG,  O.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  und  der  Wirbel- 
tiere. Jena,  1906. 

His,  W.:  Zur  Bildungsgeschichte    der  Lungen  beim  menschlichen  Embryo.     Arch.  /. 
Anat.  u.  Physiol.,  Anat.  Abth.,  1887. 

KALLIUS,  E.:  Beitrage  zur  Entwickelungsgeschichte  des  Kehlkopfes.  Anat.  Hejte, 
Bd.  IX,  1897. 

KOLLMANN,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1907. 


THE  DEVELOPMENT  OF  THE  RESPIRATORY  SYSTEM.  369 

McMuRRiCH,  J.  P.:  The  Development  of  the  Human  Body.     Third  Ed.,  1907. 

PIERSOL,  G.  A.:  Teratology.  In  Wood's  Reference  Handbook  of  the  Medical  Sciences, 
Vol.  VII,  1904. 

SYMINGTON,  J.:  On  the  Relations  of  Larynx  and  Trachea  to  the  Vertebral  Column  in 
the  Foetus  and  Child.  Journ.  of  Anat.  and  PhysioL,  Vol.  IX. 


CHAPTER  XIV. 

THE  DEVELOPMENT  OF  THE  CGELOM  (PERICARDIAL 

PLEURAL  AND  PERITONEAL  CAVITIES),  THE 

PERICARDIUM,  PLEUROPERITONEUM, 

DIAPHRAGM,  AND  MESENTERIES. 

In  the  Chapter  on  the  development  of  the  germ  layers,  it  is  stated  that  the 
peripheral  part  of  the  mesoderm  splits  into  two  layers,  an  outer  or  parietal,  and 
an  inner  or  visceral  (Fig.  81;  see  also  p.  83).  The  parietal  layer  of  mesoderm 
and  the  ectoderm  constitute  the  somatopleure.  The  visceral  layer  and  the 
entcderm  constitute  the  splanchnopleure  (Fig.  81).  The  cleft  or  cavity 
that  appears  between  the  parietal  and  visceral  layers  is  the  ccelom  or  body 
cavity  and  is  lined  with  a  layer  of  flattened  mesodermal  cells  known  as  the 
mesothelium.  It  will  be  remembered  that  in  the  earlier  stages  of  development  a 
portion  of  the  embryonic  disk  becomes  constricted  off  from  the  yolk  sac  to  form 
the  simple  cylindrical  body  (p.  137).  Along  each  side  of  the  axial  portion  of  the 
germ  disk,  and  also  at  its  cephalic  and  caudal  ends,  the  germ  layers  bend  ven- 
trally  and  then  medially  until  they  meet  and  fuse  in  the  midventral  line  (p.  141). 
In  this  way  a  part  of  the  somatopleure  forms  the  lateral  and  ventral  portions  of 
the  body  wall  (Fig.  141).  At  the  same  time  the  axial  portion  of  the  entoderm  is 
bent  into  a  tube  which  is  closed  at  both  ends — the  primitive  gut — and  is  then 
pinched  off  from  the  rest  of  the  entoderm  except  at  one  point,  where  the  cavity 
of  the  gut  remains  in  communication  with  the  cavity  of  the  yolk  sac.  The 
splanchnic  mesoderm  adjacent  to  the  entoderm  on  each  side  comes  in  contact 
and  fuses  with  the  corresponding  portion  from  the  opposite  side,  thus  forming 
a  sheet  of  tissue  which  encloses  the  primitive  gut  and  also  forms  a  partition  be- 
tween the  two  parts  of  the  coelom.  This  sheet  of  tissue  is  the  common  mesentery 
and  is  attached  to  the  dorsal  and  ventral  body  walls  along  the  medial  line. 
The  portion  between  the  gut  and  the  dorsal  body  wall  is  the  dorsal  mesentery, 
the  portion  between  the  gut  and  the  ventral  body  wall  is  the  ventral  mesentery. 
Thus  the  gut  is  suspended  in  the  common  mesentery  (Figs.  235  and  320). 

When  portions  of  the  somatopleure  and  splanchnopleure  are  bent  ventrally 
the  coelom  between  the  portions  is  naturally  carried  with  them.  This  part  of 
the  coelom  thus  becomes  enclosed  within  the  cylindrical  body  and  constitutes 
the  intraembryonic  or  simply  the  embryonic  coelom  (body  cavity  proper).  The 
part  of  the  coelom  which,  while  the  germ  layers  were  still  flat,  was  situated  more 
peripherally  constitutes  the  extraembryonic  coelom  or  eococcelom  (extraembryonic 

370 


PERICARDIUM,  PLEUROPERITOXEUM,  DIAPHRAGM  AND  MESENTERIES.      371 

body  cavity).  From  the  nature  of  the  bending  process,  the  embryonic  ccelom 
is  divided  into  bilaterally  symmetrical  parts  by  the  common  mesentery  (Fig. 
235).  These  two  simple  cavities  are  the  forerunners  of  all  the  serous  cavities  of 
the  body.  The  various  partitions  between  the  serous  cavities,  the  walls  of  the 
cavities  and  the  mesenteries  proper  are  all  derived  from  the  somatic  and 
splanchnic  mesoderm  with  its  covering  of  mesothelium. 

While  the  foregoing  would  represent  a  typical  case  of  early  ccelom  and 
mesentery  formation,  there  are  certain  modifications  and  peculiarities  in  the 
higher  Mammals  and  in  man.  In  all  cases  the  splitting  of  the  mesoderm  to 
form  the  ccelom  proceeds  from  the  periphery  of  the  germ  disk  toward  the  axial 
portion  (p.  85).  In  the  human  embryo  the  bending  ventrally  and  fusing  of  the 
germ  layers  to  form  the  cylindrical  body  begins  in  the  anterior  region  of  the 
disk  and  is  accomplished  there  before  the  splitting  of  the  mesoderm  is  com- 
pleted. The  peripheral  splitting  has  resulted  in  the  formation  of  the  exoccelom, 
but  at  the  time  when  the  ventral  fusion  of  the  germ  layers  takes  place,  the  split- 
ting has  not  extended  axially  to  a  sufficient  degree  to  form  the  intraembryonic 
coelom.  The  latter,  which  appears  later  in  this  region,  never  communicates 
laterally,  therefore,  with  the  exoccelom.  Caudal  to  this  region  the  ccelom  is 
formed  as  in  the  typical  case.  The  more  anterior  part  of  the  ccelom  on  each 
side  is  thus  primarily  a  pocket-like  cavity.  It  communicates  with  the  rest  of  the 
coelom  at  about  the  level  of  the  yolk  stalk.  In  the  region  of  the  fore-gut,  the 
future  cesophagus,  no  distinct  mesentery  is  formed,  but  the  fore-gut  remains 
broadly  attached  to  the  dorsal  body  wall.  A  ventral  mesentery  is  lacking  from 
a  point  just  cranial  -to  the  yolk  stalk  to  the  caudal  end  of  the  gut.  There  are 
no  coelomic  cavities  in  the  branchial  arches,  the  ccelom  extending  only  to  the 
last  branchial  groove. 

In  very  young  human  embryos  the  primitive  segments  contain  small  cavities. 
These  cavities  soon  disappear,  being  filled  with  cells  from  the  surrounding 
parts  of  the  segments.  Whether  they  represent  isolated  portions  of  the  ccelom 
is  not  certain.  In  the  lower  Vertebrates,  the  cavities  of  the  primitive  segments 
regularly  communicate  with  the  ccelom,  and  in  the  sheep  the  cavities  of  the  first 
formed  segments  are  continuous  with  the  ccelom.  In  the  head  there  is  no 
cavity  analogous  to  the  ccelom  in  the  body.  In  but  one  human  embryo  have 
any  cavities  in  the  head  resembling  those  of  the  primitive  segments  been 
observed  (see  p.  301). 

The  Pericardial  Cavity,  Pleural  Cavities  and  Diaphragm. 

The  pericardial  and  pleural  cavities  and  diaphragm  are  so  closely  related  in 
their  development  that  they  must  be  considered  together.  In  the  region  just 
caudal  to  the  visceral  arches,  where  the  two  anlagen  of  the  heart  appear,  the 
embryonic  coelom  becomes  dilated  at  a  very  early  stage  to  form  the  primitive 
pericardial  cavity  (parietal  cavity  of  His).  After  the  two  anlagen  of  the  heart 


372 


TEXT-BOOK  OF  EMBRYOLOGY. 


unite  to  form  a  simple  tubular  structure  (p.  227;  also  Fig.  194),  the  latter  is 
suspended  in  the  cavity  by  a  mesentery  which  consists  of  a  dorsal  and  a  ventral 
part,  a  dorsal  and  a  ventral  mesocardium.  By  these  the  cavity  is  at  first  divided 
into  two  bilaterally  symmetrically  parts.  The  mesocardia  soon  disappear  and 
leave  the  heart  attached  only  to  the  large  vascular  trunks  which  suspend  it 
in  the  single  pericardial  cavity.  The  early  pericardial  cavity  is  simply  the 
cephalic  end  of  the  embryonic  ccelom  and  is  therefore  directly  continuous  with 
the  rest  of  the  ccelom.  As  mentioned  on  p.  371  it  does  not,  however,  at  any 
time  communicate  laterally  with  the  extraembryonic  coelom. 

The  communication  between  the  pericardial  cavity  and  the  rest  of  the  em- 
bryonic coelom  is  soon  partly  cut  off  by  the  development  of  a  transverse  fold 
— the  septum  transversum.  This  septum  is  formed  in  close  relation  with  the 
omphalomesenteric  veins.  These  vessels  unite  in  the  sinus  venosus  at  the 
caudal  end  of  the  heart,  whence  they  diverge  in  the  splanchnic  mesoderm. 


am 


vom 


rpr 


FIG.  329. — Transverse  sections  of  a  rabbit  embryo,  showing  how  the  omphalomesenteric  veins  (vom) 
push  outward  across  the  ccelom  and  fuse  with  the  lateral  body  wall,  forming  the  ductus 
pleuro-pericardiacus  (rp}  rpd) ;  am,  amnion.  Ravn. 

They  are  thus  embedded  in  the  mesodermal  layer  of  the  splanchnopleure,  and  as 
the  latter  closes  in  from  either  side  to  form  the  gut,  the  vessels  form  ridge-like 
projections  into  the  ccelom.  As  the  vessels  increase  in  size,  the  ridges  become 
so  large  that  the  splanchnic  mesoderm  is  pushed  outward  against  the  parietal 
mesoderm  and  fuses  with  it  (Fig.  329).  Thus  a  partition  is  formed  on  each  side, 
which  is  attached  on  the  one  hand  to  the  mesentery  and  on  the  other  hand  to  the 
ventral  and  lateral  body  walls,  and  which  contains  the  omphalomesenteric  veins. 
It  is  obvious  that  these  partitions,  forming  the  septum  transversum,  close  the 
ventral  part  of  the  communication  between  the  pericardial  cavity  and  the  rest  of 
the  coelom.  The  dorsal  part  of  the  communication  remains  open  on  each  side 
of  the  mesentery  as  the  ductus  pleuro-pericardiacus  (dorsal  parietal  recess  of  His) 
(Figs.  329  and  330). 

As  the  heart  develops  it  migrates  caudally,  and  by  corresponding  migration 
the  pericardial  cavity  draws  the  ventral  edge  of  the  septum  transversum  farther 
caudally,  so  that  the  cephalic  surface  of  the  latter  faces  ventrally  and  cranially. 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND  MESENTERIES.     373 


In  other  words  the  septum  comes  to  lie  in  an  oblique  cranio-caudal  plane.  The 
pericardial  cavity  therefore  comes  to  lie  ventral  to  the  ductus  pleuro-pericardiaci. 
The  latter — one  on  each  side  of  the  mesentery — are  two  passages  which  com- 


Pericardial  cavity 

Lateral  mesocardium  •    \ 

Pericardium 

Septum  transversum 

Liver 

Ductus  choledochus 

Yolk  stalk  -•• 


Ventral  aortic  trunk 
Dorsal  mesocardium 

Sinus  venosus 
Duct  of  Cuvier 

Left  umbilical  vein 
Left  omphalomes.  vein 
Ductus  pleuro-pericardiacus 

tomach 
Peritoneal  cavity 


Pharynx  s.      £R 

Dorsal  mesocardium  \  /,  "c-w 

}  C 


Ductus  pleuro- 
pericardiacus 


FIG.  330. — From  a  model  of  the  septum  transversum,  liver,  etc.,  of  a  human  embryo 
of  3  mm.     His,  K oilman. 

municate  on  the  one  hand  with  the  pericardial  cavity  and  on  the  other  hand  with 
the  peritoneal  cavity ,-  while  they  themselves  form  the  cavities  into  which  the  lungs 
grow — the  pleural  cavities.  (Compare  Figs.  330,  331  and  332.) 


Aorta 


Ductus  pleuro- 
pericardiacus 
Duct  of  Cuvier 


Heart 


s>^--— ^         Pericardial  cavity 

FIG.  331. — View  (in  perspective)  of  the  pcricardial  cavity  and  ductus  pleuro-pericardiaci 
of  a  rabbit  embryo  of  9  days.     Ravn. 

The  pleural  cavities  also  become  separated  from  the  pericardial  cavity,  ap- 
parently through  the  agency  of  the  ducts  of  Cuvier.  The  anterior  and  posterior 
cardinal  veins  on  each  side  unite  to  form  the  duct  of  Cuvier  which  then  extends 


374 


TEXT-BOOK  OF  EMBRYOLOGY. 


from  the  body  wall  through  the  dorsal  free  edge  of  the  septum  transversum  to 
join  the  sinus  venosus  (Fig.  330).  This  free  edge  is  pushed  farther  and 
farther  into  the  ductus  pleuro-pericardiacus  (Fig.  331)  until  it  meets  and  fuses 


Pleural  cavity 


\ 


\  Dorsal  mesentery 


^fj:, 

C" 


Lateral  mesocardium — »• 


Pericardial  cavity 


___  Lateral  mesocardium 

Dorsal  mesocardium 
Heart 


FIG.  332. — View  (in  perspective)  of  the  pericardia!  and  plcural  cavities  of  a  human  embryo 

of  7.5  mm.     Kollmann. 

The  arrow  points  through  the  opening  which  forms  the  communication  between  the  pleural 
and  peritoneal  cavities,  and  which  is  eventually  closed  by  the  pleuro-peritoneal  membrane. 

with  the  mesentery  or  posterior  mediastinum.     This  process  thus  produces  a 
septum  between  each  pleural  cavity  and  the  pericardial  cavity. 

The  septum  transversum  early  acquires  still  more  complicated  relations 


Lung 


Pleuro-peritoneal  membrane 


Mesentery  of  i __, 

inf.  vena  cava  i    " 


Inferior  vena  cava 


Mesonephros   •-V   jig 


Lung 

ii  Pleuro-peritoneal  membrane 
^Mesentery 

1 

"^  P1  euro-peritoneal  membrane 
- 1  CEsophagus 


-.' —  Dorsal  mesogastrium 


FIG.  333. — Ventral  view  (in  perspective)  of  parts  of  the  lungs,  pleural  cavities,  peritoneal  cavity, 
and  the  pleuro-peritoneal  membranes  in  a  rat  embryo.     Ravn. 

from  the  fact  that  the  liver  grows  into  its  caudal  part  (Fig.  330) .  It  may,  for  this 
reason,  be  divided  into  a  caudal  part  in  which  the  liver  is  situated  and  which 
furnishes  the  fibrous  capsule  (of  Glisson)  and  the  connective  tissue  of  the  liver, 
and  a  cephalic  part  which  may  be  called  the  primary  diaphragm.  These  two 
parts  at  first  are  not  separate,  the  separation  taking  place  secondarily.  After 


PERICARDIUM,  PLEUROPERITOXEUM,  DIAPHRAGM  AND  MESENTERIES.      375 


the  separation  between  the  pericardial  cavity  and  the  pleural  cavities,  the  latter 
for  a  time  remain  in  open  communication  with  the  rest  of  the  ccelom  or  peritoneal 
cavity.  The  lungs,  as  they  develop,  grow  into  the  pleural  cavities  (Fig.  332) 
until  their  tips  finally  touch  the  cephalic  surface  of  the  liver.  At  this  point 
folds  grow  from  the  lateral  and  dorsal  body  walls  (Fig.  333)  and  unite  ventrally 
with  the  primary  diaphragm  and  medially  with  the  mesentery.  These  folds — 
the  pleuroperitoneal  membranes — separate  the  pleural  cavities  from  the  perit- 
oneal cavity  and  complete  the  diaphragm.  Thus  the  diaphragm,  from  the  stand- 


a-  PL  cav. 


p.m. 


PC.  cav. 


Lv.c. 


FIG.  335. 

FIG.  334. — Transverse  section  through  the  thoracic  region  of  a  rabbit  embryo  of  15  days.  Hochstetter. 
FIG.  335. — Transverse  section  through  the  thoracic  region  of  a  cat  embryo  of  25  mm.  Hochstetter. 
I.v.c..  Inferior  vena  cava;  Inf.-c.  1.,  infracardiac  lobe  of  lung;  L.t  lung;  Oe..  oesophagus;  PC.  cav., 

pericardial  cavity;  PI.  cav.,  pleural  cavity;  Pl.-p.  m.,  pleuro- pericardial  membrane;  Pu.-h.  r.t 

pulmo-hepatic  recess. 

point  of  development,  consists  of  two  parts :  a  ventral  part  which  is  the  cephalic 
portion  of  the  original  septum  transversum,  and  a  dorsal  part  which  develops 
later  from  the  body  wall  and  is  the  closing  membrane  between  the  peritoneal 
and  pleural  cavities.  The  musculature  of  the  diaphragm  is  considered  in  the 
chapter  on  the  muscular  system  (p.  300). 

While  the  foregoing  structures  are  being  formed,  decided  changes  take  place 
in  their  positions  and  relations.  At  first  the  heart  lies  far  forward  in  the  cervi- 
cal region  near  the  visceral  arches.  Later  it  migrates  caudally  and  the  pericardial 


376 


TEXT-BOOK  OF  EMBRYOLOGY. 


cavity  comes  to  occupy  much  of  the  ventral  part  of  the  thorax,  the  pericardium 
having  extensive  attachments  to  the  ventral  body  wall  and  to  the  cephalic  sur- 
face of  the  primary  diaphragm  (Fig.  330).  The  diaphragm  is  much  farther 
forward  than  in  the  adult  and  is  broadly  attached  to  the  cephalic  surface  of  the 
liver.  The  principal  changes  which  bring  about  the  adult  conditions  are  the 
growth  of  the  lungs,  the  separation  of  the  diaphragm  from  the  liver,  and  the 

caudal  migration  of  the  diaphragm  itself.  With 
the  development  of  the  lungs,  the  pleural  cavities 
necessarily  enlarge  and  push  their  way  ventrally. 
In  so  doing  they  split  the  pericardium  away  from 
the  lateral  body  walls  and  likewise  from  the  dia- 
phragm (compare  Figs.  334  and  335).  Thus  the 
pericardial  cavity  comes  to  be  confined  more  and 
more  closely  to  the  medial  ventral  position.  The 
separation  of  the  liver  from  the  primary  diaphragm 
is  caused  by  changes  in  the  peritoneum  which  at 
first  covers  the  caudal,  lateral  and  ventral  surfaces 
of  the  liver.  The  cephalic  surface  of  the  liver,  as 
stated  above,  is  covered  by  the  primary  diaphragm 
itself.  The  peritoneum  is  reflected  from  the  surface 
of  the  liver  on  to  the  diaphragm,  and  at  the  line  of 
reflection  a  groove  appears  on  each  side,  extending 
from  the  midventral  line  around  as  far  as  the 
attachment  of  the  liver  to  the  diaphragm.  The 
FIG.  336.— Diagram  showing  the  grooves  gradually  grow  deeper,  the  peritoneum 
human^e^br^^^F^lerent  pushing  its  way,  as  a  flat  sac,  between  the  two 
stages.  Mall.  structures,  until  the  separation  is  almost  complete. 

The  positions  are  those  shown  . 

in  embryos  of  Mall's  collection    There   is   left,    however,    an   area  of  attachment 
(except  KO,  which  is  a  10.2   between  the  liver  and  diaphragm,  over  which  the 

mm.  embryo  of  the  His  collec-  m  f  r 

tion) ;  xii  being  an  embryo  of   peritoneum  is  reflected,  the  ligamenlum  coronarium 

In  the  medial  line  there  is  also  left  a 


ix,  of  17  mm.;  XLin,  of  15    broad  thin  lamella  which  is  attached  to  the  dia- 

mm.;   VI,  of  24  mm.      The 

numerals  on  the  right  indicate    phragm,  the  liver  and  the  ventral  body  wall.     This 

is  a  remnant  of  the  ventral  mesentery  and  forms 

the  ligamenlum  suspensorium  (falciforme)  hepatis.  In  its  free  caudal  edge 
is  embedded  the  ligamentum  teres  hepatis  which  is  closely  related  to  the 
umbilical  vein  (see  p.  261).  The  diaphragm  itself,  during  its  development, 
migrates  from  a  position  in  the  cervical  region,  where  the  septum  transversum 
first  appears,  to  its  final  position  opposite  the  last  thoracic  vertebrae.  During 
the  migration  the  plane  of  direction  also  changes  several  times,  as  may  be 
seen  in  Fig.  336. 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND  MESENTERIES.     377 

The  Pericardium  and  Pleura. — Since  the  pericardial  cavity  represents  a 
portion  of  the  original  ccelom,  the  lining  of  the  cavity  must  be  a  derivative  of 
either  the  parietal  or  the  visceral  layer  of  mesoderm  or  of  both.  The  common 
mesentery  in  which  the  heart  develops  is  derived  from  the  visceral  layer.  Con- 
sequently the  epicardium  is  a  derivative  of  the  visceral  mesoderm  (Fig.  203). 
The  pericardium  is  derived  from  three  regions  of  mesoderm.  The  greater 
part  is  derived  from  the  parietal  mesoderm,  since  the  body  wall  which  is  com- 
posed of  parietal  mesoderm  is  also  primarily  the  wall  of  the  pericardial  cavity. 
A  small  dorsal  portion  is  probably  derived  from  the  mesoderm  at  the  root  of  the 
dorsal  mesocardium  (Fig.  203).  The  septum  transversum  primarily  forms 
the  caudal  wah1  of  the  pericardial  cavity,  and,  since  the  septum  is  a  derivative 
of  the  visceral  layer,  the  caudal  wall  is  derived  from  this  layer.  The  three 
portions  are,  of  course,  continuous. 

The  lungs  first  appear  in  the  common  mesentery  as  an  evagination  from  the 
primitive  gut  (Fig.  320,  p.  360).  As  they  develop  further  they  grow  into  the 
pleural  cavities,  pushing  a  part  of  the  mesentery  before  them.  This  part  of 
the  mesentery  thus  invests  the  lungs  and  forms  the  visceral  layer  of  the  pleura 
which  is  therefore  a  derivative  of  the  visceral  mesoderm.  The  parietal  layer  of 
the  pleura  is  a  derivative  of  the  parietal  mesoderm,  since  the  wall  of  the  pleural 
cavity  is  primarily  the  body  wall. 

The  lining  of  all  these  cavities  is  at  first  composed  of  mesothelium  and 
mesenchyme.  The  latter  is  transformed  into  the  delicate  connective  tissue  of 
the  serous  membranes,  and  the  mesothelium  becomes  the  mesothelium  of 
the  membranes. 

The  Omentum  and  Mesentery. 

From  the  septum  transversum  (or  diaphragm)  to  the  anus  the  gut  is  sus- 
pended in  the  ccelom  (or  abdominal  cavity)  by  means  of  the  dorsal  mesentery. 
This  is  attached  to  the  dorsal  body  wall  along  the  medial  line  and  lies  in  the 
medial  sagittal  plane  (Fig.  301;  compare  with  Fig.  235).  On  the  ventral  side  of 
the  gut  a  mesentery  is  lacking  from  the  anus  to  a  point  just  cranial  to  the  yolk 
stalk  (p.  371).  There  is,  however,  a  small  ventral  mesentery  extending  a  short 
distance  caudally  from  the  septum  transversum.  On  account  of  its  relation  to 
the  stomach  this  is  known  as  the  ventral  mesogastrium  (Fig.  301).  These  two 
sheets  of  tissue,  the  dorsal  and  ventral  mesenteries,  are  destined  to  give  rise  to 
the  omenta  and  mesenteries  of  the  adult.  Owing  to  the  enormous  elongation  of 
the  gut  and  its  extensive  coiling  in  the  abdominal  cavity,  the  primary  mesen- 
teries are  twisted  and  thrown  into  many  folds  which  enclose  certain  pockets  or 
bursas.  Furthermore,  certain  parts  of  the  gut  which  are  originally  free  and 
movable  become  attached  to  other  parts  and  to  the  body  walls  through  fusions 
of  certain  parts  of  the  mesentery  with  one  another  and  with  the  body  walls. 


378 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  Greater  Omentum  and  Omental  Bursa. — A  small  part  of  the  gut 
caudal  to  the  diaphragm  is  destined  to  become  the  stomach,  and  the  portion  of 
the  mesentery  which  attaches  it  to  the  dorsal  body  wall  is  known  as  the  dorsal 
mesogastrium  (Fig.  301).  The  latter  is  inserted  along  the  greater  curvature  of 
the  stomach  and  lies  in  the  medial  sagittal  plane  so  long  as  the  stomach  lies  in 
this  plane.  When  the  stomach  turns  so  that  its  long  axis  lies  in  a  transverse 
direction  and  its  greater  curvature  is  directed  caudally  (p.  336),  the  dorsal 
mesogastrium  changes  its  position  accordingly.  From  its  attachment  along  the 
dorsal  body  wall  it  bends  to  the  left  and  then  ventrally  to  its  attachment  along 
the  greater  curvature  of  the  stomach.  Thus  a  sort  of  sac  is  formed  dorsal  to 
the  stomach  (Figs.  337  and  338).  This  sac  is  really  a  part  of  the  abdominal  or 


Yolk  stalk 


Stomach 


Rectum 


Duodenum 


Caecum 
Appendix 
Mesentery 

Yolk  stalk 


FIG.  337. 


Stomach 


Rectum 


FIG.  338. 

FIG.  337.— Diagram  of  the  gastrointestinal  tract  and  its  mesenteries 

at  an  early  stage.     Ventral  view.     Hertwig. 
FIG.  338. — Same  at  a  later  stage      Hertwig. 
The  arrow  points  into  the  bursa  omentalis. 


peritoneal  cavity  and  opens  toward  the  right  side.  The  ventral  wall  is  formed 
by  the  stomach,  the  dorsal  and  caudal  walls  by  the  mesogastrium.  The  cavity 
of  the  sac  is  the  omental  bursa  (bursa  omentalis) ;  the  mesogastrium  forms  the 
greater  amentum  (omentum  majus) .  The  opening  from  the  bursa  into  the  general 
peritoneal  cavity  is  the  epiploic  foramen  (foramen  of  Winslow).  (Fig.  314.) 

From  the  third  month  on,  the  greater  omentum  becomes  larger  and  gradually 
extends  toward  the  ventral  abdominal  wall,  over  the  transverse  colon,  and  then 
caudally  between  the  body  wall  and  the  small  intestine  (Figs.  339  and  340). 
The  portion  between  the  body  wall  and  intestine  encloses  merely  a  flat  cavity 
continuous  with  the  larger  cavity  dorsal  to  the  stomach.  From  the  fourth 
month  on,  the  omentum  fuses  with  certain  other  structures  and  becomes  less 
free.  The  dorsal  lamella  fuses  with  the  dorsal  body  wall  on  the  left  side  and 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND  MESENTERIES.      379 


with  the  transverse  mesocolon  and  transverse  colon  (Fig.  341).  During  the 
first  or  second  year  after  birth  the  two  lamellae  fuse  with  each  other  caudal 
to  the  transverse  colon  to  form  the  greater  omentum  of  adult  anatomy. 


Diaphragm  . 


Lesser  omentum 

Pancreas 
Bursa  omentalis 

Stomach 

Greater  omentum 

Duodenum 

Transverse  mesocolon 

Transverse  colon 

Mesentery  of 
small  intestine 

Small  intestine  -----  V\~  — 


FIG.  339. 


Diaph. 


FIG.  340.  FIG.  341. 

FIGS.  339,  340  and  341. — Diagrams  showing  stages  in  the  development  of  the  bursa  omentalis,  the 
greater  omentum,  and  the  fusion  of  the  latter  with  the  transverse  mesocolon.  Diagrams 
represent  sagittal  sections.  For  explanation  of  lettering  in  Figs.  340  and  341  see  Fig.  339. 

The  Lesser  Omentum. — It  has  already  been  noted  that  the  liver  grows  into 
the  caudal  portion  of  the  septum  transversum  (p.  374).  Since  the  ventral 
mesentery  in  the  abdominal  region,  or  the  ventral  mesogastrium,  is  primarily 


380  TEXT-BOOK  OF  EMBRYOLOGY. 

directly  continuous  with  the  septum  transversum,  it  is  later  attached  to  the 
liver.  In  other  words  it  passes  between  the  liver  and  the  lesser  curvature  of  the 
stomach  and  also  extends  along  the  duodenal  portion  of  the  gut  for  a  short 
distance  (Fig.  301).  As  the  stomach  turns  to  the  left  the  ventral  mesentery  is 
also  drawn  toward  the  left  and  comes  to  lie  almost  at  right  angles  to  the  sagittal 
plane  of  the  body,  forming  the  lesser  omentum  (omentum  minus)  or  the  hepato- 
gastric  and  hepatoduodenal  ligaments  of  the  adult  (Figs.  341  and  342). 

The  Mesenteries. — So  long  as  the  intestine  is  a  straight  tube,  the  dorsal 
mesentery  lies  in  the  medial  sagittal  plane,  its  dorsal  attachment  being  practi- 
cally of  the  same  length  as  its  ventral  (intestinal)  attachment.  As  development 
proceeds,  the  intestine  elongates  much  more  rapidly  than  the  abdominal  walls, 
and  the  intestinal  attachment  of  the  mesentery  elongates  accordingly.  When 
the  portion  of  the  intestine  to  which  the  yolk  stalk  is  attached  grows  out  into  the 
proximal  end  of  the  umbilical  cord  (p.  338),  the  corresponding  portion  of  the 
mesentery  is  drawn  out  with  it  (Fig.  301).  When  the  intestine  returns  to  the 
abdominal  cavity  and  forms  the  primary  loop,  with  the  caecum  to  the  right  side 
(p.  339),  its  mesenteric  attachment  is  carried  out  of  the  medial  sagittal  plane. 
This  results  in  a  funnel-shaped  twisting  of  the  mesentery  (Figs.  337  and  338). 
The  portion  of  the  mesentery  which  forms  the  funnel  is  destined  to  become  the 
mesentery  of  the  jejunum,  ileum,  and  ascending  and  transverse  colon,  and  is 
attached  to  the  dorsal  body  wall  at  the  apex  of  the  funnel  (Fig.  337,  338,  342). 
This  condition  is  reached  about  the  middle  of  the  fourth  month. 

Up  to  this  time  the  mesentery  and  intestine  are  freely  movable,  that  is,  they 
have  formed  no  secondary  attachments.  From  this  time  on,  as  the  intestine 
continues  to  elongate  and  forms  loops  and  coils,  the  mesentery  is  thrown  into 
folds,  and  certain  parts  of  it  fuse  with  other  parts  and  with  the  body  wall. 
Thus  certain  parts  of  the  intestine  become  less  free  or  less  movable  within  the 
abdominal  cavity. 

The  duodenum  changes  from  the  original  longitudinal  position  to  a  more 
nearly  transverse  position  and,  with  its  mesentery — the  mesoduodenum — fuses 
with  the  dorsal  body  wall,  thus  becoming  firmly  fixed.  Since  the  mesoduode- 
num fuses  with  the  body  wall,  the  duodenum  has  no  mesentery  in  the  adult. 
The  pancreas,  which  is  primarily  enclosed  within  the  mesoduodenum,  also 
becomes  firmly  attached  to  the  dorsal  body  wall  (compare  Figs.  339  and  340). 

The  mesentery  of  the  transverse  colon,  or  the  transverse  mesocolon,  which 
lies  across  the  body  ventral  to  the  duodenum  (Figs.  338  and  342),  fuses  with  the 
ventral  surface  of  the  latter  and  with  the  peritoneum  of  the  dorsal  body  wall. 
In  this  way  the  dorsal  attachment  of  the  transverse  mesocolon  is  changed  from 
its  original  sagittal  direction  to  a  transverse  direction  (Figs.  340  and  341).  The 
mesocolon  itself  forms  a  transverse  partition  which  divides  the  peritoneal  cavity 
into  two  parts,  an  upper  (or  cranial)  which  contains  the  stomach  and  liver,  and 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND  MESENTERIES.      381 

a  lower  (or  caudal)  which  contains  the  rest  of  the  digestive  tube  except  the 
duodenum.  The  mesentery  of  the  duodenum  and  pancreas  changes  from  a 
serous  membrane  into  subserous  connective  tissue,  and  these  two  organs  as- 
sume the  retroperitoneal  position  characteristic  of  the  adult  (Fig.  339). 

The  mesentery  of  the  descending  colon,  or  the  descending  mesocolon,  lies  in 
the  left  side  of  the  abdominal  cavity,  in  contact  with  the  peritoneum  of  the  body 
wall  (see  Fig.  342).  It  usually  fuses  with  the  peritoneum,  and  the  descending 


Dors,  mesogastrium 


Lesser  omentum 
(hep.-gast.  Kg.) 


Bile  duct 


Mesoduodenum        


Transv.  colon 


Spleen 


Duo.-jej.  flexure 

Desc.  colon 
Desc.  mesocolon 


Appendix 


Yolk  stalk 


Medial  line 

FIG.  342. — Gastrointestinal  tract  and  mesenteries  in  a  human  embryo.     The  arrow 
points  into  the  bursa  omentalis.     Kollmann. 


colon  thus  becomes  fixed.  After  the  ascending  colon  is  formed,  the  ascending 
mesocolon  usually  fuses  with  the  peritoneum  on  the  right  side  (see  Fig.  342).  In 
a  large  percentage  (possibly  25  per  cent.)  of  individuals,  the  fusion  between  the 
peritoneum  and  the  ascending  and  descending  mesocolon  is  incomplete  or 


wanting. 


The  sigmoid  mesocolon  bends  to  the  left  to  reach  the  sigmoid  colon,  but 
forms  no  secondary  attachments.  It  is  continuous  with  the  mesorectum  which 
maintains  its  original  sagittal  position.  A  sheet  of  tissue — the  mesoappendix — • 
continuous  with  and  resembling  the  mesentery,  is  attached  to  the  cascum  and 
vermiform  appendix  (Fig.  342).  It  probably  represents  a  drawn  out  portion  of 


382  TEXT-BOOK  OF  EMBRYOLOGY. 

the  original  common  mesentery,  since  the  caecum  and  appendix  together  are 
formed  as  an  evagination  from  the  primitive  gut. 

Normally  the  mesentery  of  the  small  intestine  forms  no  secondary  attach- 
ments, but  is  thrown  into  a  number  of  folds  which  correspond  to  the  coils  of  the 
intestine. 

The  secondary  attachments  of  the  greater  omentum  and  the  fusion  of  the 
two  lamellae  have  been  described  earlier  in  this  chapter  (p.  378).  The  mesen- 
teries of  the  urogenital  organs  are  considered  in  connection  with  the  develop- 
ment of  those  organs  (Chapter  XV). 

The  Peritoneum. — The  thin  layer  of  tissue — composed  of  delicate  fibrous 
connective  tissue  and  mesothelium — which  lines  the  abdominal  cavity  and  is  re- 
flected over  the  various  omenta,  mesenteries  and  visceral  organs,  is  derived 
wholly  from  the  mesoderm.  The  lining  of  the  coelom  is  composed  of  mesothe- 
lium and  mesenchyme.  The  latter  gives  rise  to  the  connective  tissue  of  the 
serous  membranes,  and  the  mesothelial  layer  becomes  the  mesothelium  of  these 
membranes. 

Anomalies. 

THE  PERICARDIUM. — Anomalous  conditions  of  the  pericardium  are  usually, 
although  not  necessarily,  associated  with  anomalies  of  the  heart.  They  may 
also  be  associated  with  defects  in  the  diaphragm.  Displacement  of  the  heart 
(ectopia  cordis)  is  accompanied  by  displacement  of  the  pericardium.  The 
heart  sometimes  protrudes  through  the  thoracic  wall,  and,  as  a  rule,  in  such  cases 
is  covered  by  the  protruding  pericardium.  In  extensive  cleft  of  the  thoracic 
wall  (thoracoschisis,  Chap.  XIX)  the  pericardium  may  be  ruptured. 

THE  DIAPHRAGM. — The  most  common  malformation  of  the  diaphragm  is  a 
defect  in  its  dorsal  part,  occurring  much  more  frequently  on  the  left  than  on  the 
right  side.  The  defect  may  affect  but  a  small  portion  or  may  be  extensive,  the 
peritoneum  being  directly  continuous  with  the  parietal  layer  of  the  pleura. 
Such  defects  are  due  to  the  imperfect  development  of  the  pleuro-peritoneal  mem- 
brane which  normally  grows  from  the  dorso-lateral  part  of  the  body  wall  and 
fuses  with  the  edge  of  the  primary  diaphragm,  thus  separating  the  pleural  and 
and  peritoneal  cavities  (p.  375).  The  most  conspicuous  result  of  defects  in  the 
dorsal  part  of  the  diaphragm  is  diaphragmatic  hernia,  in  which  parts  of  the 
stomach,  liver,  spleen  and  intestine  project  into  the  pleural  cavity,  either  free  or 
enclosed  in  a  peritoneal  sac.  Defects  in  the  ventral  part  of  the  diaphragm,  due 
to  imperfect  development  of  portions  of  the  septum  transversum,  are  not 
common. 

THE  MESENTERIES  AND  OMENTA. — Extensive  malformations  of  the  mesen- 
teries apparently  do  not  occur  without  extensive  malformations  of  the  digestive 
tract.  One  of  the  most  striking  anomalous  conditions  is  a  retained  embryonic 


PERICARDIUM,  PLEUROPERITONEUM,  DIAPHRAGM  AND  MESENTERIES.      333 

simplicity  of  the  mesentery,  concurrent  with  corresponding  simplicity  in  the 
loops  and  coils  of  the  intestine.  In  this  anomaly  the  intestine  has  failed  to 
arrive  at  its  usual  complicated  condition  and  the  mesentery  has  not  undergone 
the  usual  processes  of  folding  and  fusion  (p.  380  et  seq.).  Minor  variations  in 
the  mesenteries  and  omenta  are  probably  due  largely  to  imperfect  fusion  of 
certain  parts  with  one  another  and  with  the  body  wall.  It  is  not  uncommon  to 
find  the  ascending  or  descending  colon,  or  both,  more  or  less  free  and  mov- 
able. This  condition  is  due  to  imperfect  fusion  of  the  mesocolon  with  the  body 
wall  (p.  381).  If  the  greater  omentum  is  wholly  or  partially  divided  into  sheets 
of  tissue,  the  two  primary  lamellae  have  failed  to  fuse  completely  (p.  379). 
This  divided  condition  is  normal  in  many  Mammals. 

References  for  Further  Study. 

BRACKET,  A.:  Recherches  sur  le  developpement  du  diaphragme  et  du  foie.  Jour,  de 
VAnat.  et  de  la  Physiol.,  T.  XXXII,  1895. 

BROMAX,  J. :  Die  Entwickelungsgeschichte  der  Bursa  omentalis  und  ahnlicher  Recess- 
bildungen  bei  den  Wirbeltieren.  Wiesbaden,  1904. 

BROMAX,  I.:  Ueber  die  Entwickelung  und  Bedeutung  der  Mesenterien  und  der  Korper- 
hohlen  bei  den  Wirbeltieren.  Ergebnisse  der  Anat.  u.  Entwick.,  Bd.  XV,  1906. 

BROSSIKE,  G.:  Ueber  intraabdominale  (retroperitoneale)  Hernien  und  Bauchfelltaschen, 
nebst  einer  Darstellung  der  Entwickelung  peritonealer  Formationen.  Berlin,  1891. 

HERTWIG,  O.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  und  der  Wirbeltiere. 
Jena,  1906. 

KEIBEL,  F.,  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  Vol.  I,  1910. 

KLAATSCH:  Zur  Morphologic  der  Mesenterialbildungen  am  Darmkanal  der  \Virbeltiere. 
Morph.  Jahrbuch,  Bd.  XVIII,  1892. 

KOLLMAXX,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMAXX,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Bd.  II,  1907. 

MALL,  F.  P.:  Development  of  the  Human  Ccelom.    Jour,  of  Morphol.,  Vol.  XII,  1897. 

PIERSOL.  G.  A.:  Teratology.  In  Wood's  Reference  Handbook  of  the  Medical  Sciences. 
1904. 

RAVX,  E.:  Ueber  die  Bildung  der  Scheidewand  zwischen  Brust-  und  Bauchhohle  in 
Saugetierembryonen.  Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1889. 

STRAHL  and  CARIUS:  Beitrage  zur  Entwickelungsgeschichte  des  Herzens  und  der 
Korperhohlen.  Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1889. 

SWAEX,  A.:  Recherches  sur  le  developpement  du  foie,  du  tube  digestif,  de  Parriere- 
cavite  du  peritoine  et  du  mesentere.  Premiere  partie,  Lapin.  Jour,  de  VAnat.  et  de  la 
Physiol.,  T.  XXXIII,  1896.  Seconde  partie.  Embryons  humains.  T.  XXXIII,  1897. 

TOLDT,  C.:  Bau  und  Wachstumsveranderung  der  Gekrose  des  menschlichen  Darm- 
kanals.  Denkschr.  der  kais.  Akad.  Wissensch.  Wien.  Math.-Naturivissen.  Classe,  Bd. 
XLI,  1879. 


CHAPTER  XV. 
THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 

No  other  system  in  the  body  presents  such  peculiarities  of  development  as 
the  urogenital  system.  In  the  first  place,  it  is  exceedingly  complicated  on  ac- 
count of  its  many  parts.  It  is  derived  from  both  mesoderm  (mesothelium  and 
mesenchyme)  and  entoderm.  The  urinary  portion  develops  into  a  great  com- 
plex of  ducts  for  the  carrying  off  of  waste  products.  The  genital  portion  in 
both  sexes  becomes  highly  specialized  for  the  production  and  carrying  off 
of  the  sexual  elements.  In  the  second  place,  instead  of  one  set  of  urinary  organs 
developing  and  persisting,  three  sets  develop  at  different  stages.  The  first 
set  (the  pronephroi)  disappears  in  part,  but  leaves  certain  structures  which  are 
used,  so  to  speak,  in  the  development  of  the  second.  The  second  set  (the  meso- 
nephroi)  disappears  for  the  most  part,  leaving,  however,  some  portions  which 
are  taken  up  in  the  development  of  the  genital  organs  and  other  portions  which 
persist  as  rudimentary  structures  in  the  adult.  The  third  set  (the  metanephroi 
or  kidneys)  develops  in  part  from  the  second  and  in  part  is  of  independent 
origin.  These  conditions  afford  one  of  the  most  striking  examples  of  the  repe- 
tition of  the  phylogenetic  history  by  the  ontogenetic,  or,  in  other  words,  of  von 
Baer's  law  that  an  individual,  in  its  development,  has  a  tendency  to  repeat  its 
ancestral  history;  for  the  first  and  second  sets  of  urinary  organs  in  the  human 
embryo  represent  systems  that  are  permanent  in  the  lower  Vertebrates.  In  the 
third  place,  the  ducts  of  the  genital  organs  are  not  homologous  in  the  two  sexes. 
In  the  male  the  ducts  (deferent  duct,  duct  of  the  epididymis,  efferent  ductules) 
are  derived  from  the  second  set  of  urinary  organs;  in  the  female  they  (the 
oviducts)  are  derived  from  other  ducts  which  develop  in  the  second  set  of 
urinary  organs,  but  which  are  not  functionally  a  part  of  the  latter. 

THE  PRONEPHROS. 

The  pronephros,  with  the  pronephric  duct,  is  the  first  of  the  urinary  organs 
to  appear.  In  embryos  of  2-3  mm.  there  are  two  pronephric  tubules  on  each 
side,  situated  at  the  level  of  the  heart.  Although  their  mode  of  origin  has  not 
been  observed  in  the  human  embryo,  it  is  probable,  judging  from  observations 
on  lower  Vertebrates,  that  they  arise  as  evaginations  of  the  mesothelium.  The 
part  of  the  mesothelium  involved  is  that  adjacent  to  the  intermediate  cell  mass 
(Fig.  343) .  (The  intermediate  cell  mass  is  the  portion  of  the  mesoderm  interven- 
ing between  the  primitive  segments  and  the  unsegmented  parietal  and  visceral 

384 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


385 


layers;  p.  84.)  The  more  cephalic  of  the  two  tubules  becomes  hollow  and 
opens  into  the  coelom;  the  more  caudal  is  merely  a  solid  cord  of  cells.  Neither 
tubule  forms  any  connection  with  the  pronephric  duct.  At  each  side  of  the  root 
of  the  mesentery  a  small  elevation,  which  projects  into  the  ccelom,  probably 
represents  a  rudimentary  glomerulus.  A  glomerulus  in  the  lower  Vertebrates, 
where  the  pronephros  develops  to  a  much  greater  degree  than  in  Mammals, 
contains  tortuous  vessels  derived  from  branches  of  the  aorta  (Fig.  344). 
The  mesonephros  (p.  389),  beginning  to  develop  almost  as  soon  as  the  pro- 
nephros and  in  the  same  relative  position,  forms  a  ridge  which  projects  into  the 
coelom.  The  pronephric  tubules  thus  become  embedded  in  the  mesonephric 
ridge. 

The  pronephric  duct  begins  to  develop  about  the  same  time  as  the  tubules. 
It  appears  as  a  longitudinal  ridge  on  the  outer  side  of  the  intermediate  cell  mass 

Sclerotorne       Myotome 


Ectoderm 

Parietal 

mesodenn 


Visceral 
mesoderm 


Entodenrr 


Pronephric 
tubule 


FIG.  343. — Transverse  section  of  a  dog  embryo  with  19  primitive  segments.     Bonnet. 
Section  taken  through  sixth  segment. 


at  the  level  of  the  heart  and  projects  into  the  space  between  the  mesoderm  and 
ectoderm.  The  ridge  is  at  first  solid  but  soon  acquires  a  lumen,  and  gradually 
extends  to  the  caudal  end  of  the  embryo  where  it  bends  medially  to  open  into 
the  gut.  The  origin  of  the  caudal  portion  of  the  duct  is  a  matter  of  dispute. 
It  comes  in  contact  and  fuses  with  the  ectoderm,  but  whether  in  the  higher  ani- 
mals the  fusion  is  secondary  or  signifies  a  derivation  from  the  ectoderm  has 
not  been  determined.  When  first  formed,  the  entire  duct  lies  on  the  outer  side 
of  the  intermediate  cell  mass,  but  later  becomes  embedded  in  the  mesonephric 
ridge. 

The  pronephric  tubules  are  but  transient  structures  and  have  no  functional 
significance  in  man  and  the  higher  Vertebrates.  The  ducts,  however,  remain 
and  become  the  ducts  of  the  second  set  of  urinary  organs,  the  mesonephroi. 

The  significance  of  the  pronephros  can  be  understood  only  by  reference  to  the  conditions 
in  the  lower  animals.  In  the  latter  the  pronephros  acquires  a  relatively  higher  degree  of  de« 


386  TEXT-BOOK  OF  EMBRYOLOGY. 

velopment  than  in  the  higher  forms.  The  tubules  are  segmentally  arranged  and  are  present 
in  many  segments  of  the  body.  They  open  at  their  outer  ends  into  the  ducts,  and  at  their 
inner  ends  into  the  ccelom  through  ciliated  funnel-shaped  mouths  or  nephrostomes.  Little 
masses  of  mesoderm,  containing  tortuous  vessels  derived  from  branches  of  the  aorta,  form 
glomeruli  which  project  into  the  ccelom.  Waste  products  are  removed  from  the  blood 
through  the  agency  of  the  glomeruli  and  are  collected  in  the  ccelom.  They  are  then  taken  up 
by  the  pronephric  tubules  and  carried  away  by  the  ducts.  In  some  of  the  Round  Worms 
there  is  not  even  a  longitudinal  duct,  but  the  tubules  open  directly  on  the  outer  surface  of 
the  body.  In  the  lowest  Fishes  all  the  tubules  on  each  side  open  into  a  longitudinal  duct 
which  opens  into  the  cloaca.  In  these  lower  forms  of  animal  life  the  pronephroi  constitute 
the  permanent  urinary  apparatus.  In  the  ascending  scale  the  mesonephroi  appear  (higher 


x-x  .  u^.,'  r^ 

Pron.  t.  - 


Glom. 


FIG.  344. — Diagram  of  the  pronephric  system  in  an  amphibian.     Bonnet. 

C&L,  Coelom;  Glom.,  glomerulus,  containing  ramifications  of  a  branch  of  the  aorta; 

Nch.,  notochord;  Pron.  t.,  pronephric  tubule. 

Fishes,  Amphibia)  and  assume  the  function  of  carrying  off  waste  products.  The  prone- 
phroi also  develop,  but  to  a  lesser  degree.  Still  higher  in  the  scale  (Reptiles,  Birds,  Mam- 
mals) the  kidneys  (metanephroi)  appear  and  the  mesonephroi  lose  their  functional  sig- 
nificance. But  even  in  the  very  highest  Mammals  the  pronephroi  appear,  in  a  very  rudimen- 
tary form,  in  each  individual  in  the  earliest  embryonic  stages,  thus  repeating  the  ancestral 
history. 

THE  MESONEPHROS. 

The  mesonephroi,  which  constitute  the  second  set  of  urinary  organs,  appear 
in  embryos  of  2.6-3.0  mm.,  immediately  following  the  pronephroi.  They  be- 
gin to  develop  just  caudal  to  the  pronephric  tubules  and  in  the  same  relative 
position  as  the  latter,  that  is,  in  the  intermediate  cell  mass.  Condensations* 
appear  in  the  mesenchyme  and  become  more  or  less  tortuous.  At  their  inner 
ends  they  form  secondary  connections  with  the  mesothelium  and  at  their  outer 
ends  they  join  the  pronephric  duct  which  now  becomes  the  mesonephric  (or 
Wolffian)  duct.  The  cells  acquire  an  epithelial  character,  lumina  appear, 
and  the  tortuous  mesenchymal  condensations  thus  become  true  tubules.  Their 
connections  with  the  mesothelium  soon  disappear  (Fig.  345). 

*The  term  "  condensation "  is  here  used  to  mean  increased  density  of  tissue  due  mainly  to 
proliferation  of  cells. 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


387 


After  the  tubules  are  formed,  other  condensations  of  the  mesenchyme  appear 
near  their  inner  ends.  A  branch  from  the  aorta  enters  each  condensation  and 
breaks  up  into  a  number  of  smaller  vessels  which  ramify  inside,  the  entire 
structure  thus  becoming  a  glomerulus.  Each  glomerulus  pushes  against  the 
corresponding  tubule,  the  latter  becoming  flattened  and  then  growing  around 
the  glomerulus.  In  this  way  the  glomerulus  becomes  surrounded  by  two  layers 
of  epithelium,  except  at  the  point  where  the  vessels  enter,  and  the  whole  structure 
—the  Malpighian  corpuscle — resembles  very  closely  a  renal  corpuscle  of  the  adult 

Roof        Spinal 

plate      ganglion       Amnion 


Glomerulus 


Mesentery 


Intestine 


Post,  cardinal  vein 


Mesonephric 
(Wolffian)  duct 


Blood  vessel 

Mesonephric 
(Wolffian)  ridge 


Coelom 

Body  wall  with 
umbilical  vein 


FIG.  345. — From  a  transverse  section  of  a  sheep  embryo  of  21  days  (15  mm.), 
showing  the  developing  mesonephros.     Bonnet. 


kidney.  Waste  products  are  removed  from  the  blood  through  the  agency  of 
the  glomeruli  and  are  carried  to  the  ducts  by  the  mesonephric  tubules  (Fig.  345). 
The  tubules  themselves  increase  in  length  and  become  much  coiled.  Sec- 
ondary and  tertiary  tubules  also  develop  and  become  branches  of  the  primary. 
Whether  these  develop  from  condensations  of  the  mesenchyme  or  as  buds  from 
the  primary  tubules  has  not  been  determined.  Each  tubule  consists  of  two 
parts — (i)  a  dilated  part  around  the  glomerulus,  composed  of  large  flat  cells 
and  forming  Bowman's  capsule,  and  (2)  a  narrower  coiled  part  leading  from 


388  TEXT-BOOK  OF  EMBRYOLOGY. 

the  glomerulus  to  the  duct  and  composed  of  smaller  cuboidal  cells  (Fig.  345). 
The  primary  mesonephric  tubules  are  arranged  segmentally,  one  appearing 
in  each  segment  as  far  back  as  the  pelvic  region.  Thus  the  intermediate  cell 
mass  may  be  considered  as  a  series  of  nephrotomes,  corresponding  to  the 
sclerotomes  and  myotomes.  The  segmental  character  is  soon  lost,  however, 
owing  to  the  inequality  of  growth  between  the  mesonephros  and  the  other  seg- 
mental structures,  and  to  the  development  of  the  secondary  and  tertiary  tubules. 
As  stated  above,  the  first  mesonephric  tubules  appear  immediately  caudal  to 


Mid-brain 


B^  -Fore-brain 
Hind-brain 

Branchial  groove  I 


Heart- 

i 

-  Lung 

f  V-fiPJF     '  •     '"    1  -.  -•'  ' 

Intestine 


Mesonephros- 

ffl Genital  ridge 

Coelom tH^Ki^k 

V  \  HK3B&  .  t 

j*-:£/  Body  wall 


Lower  limb  bud 

Tail 


FIG.  346. — Human  embryo  of  5  weeks.     The  ventral  body  wall  has  been  removed 
to  disclose  the  mesonephroi.     Kollmann. 

the  pronephros.  From  this  point  their  formation  gradually  progresses  in  a 
caudal  direction  as  far  as  the  pelvic  region.  By  the  further  development  of  the 
primary  and  by  the  addition  of  the  secondary  and  tertiary  tubules  and  the 
glomeruli,  the  mesonephros  as  a  whole  increases  in  size  and  forms  a  large 
structure  which  projects  into  the  ccelom  on  each  side  of  the  body,  forming  the 
so-called  mesonephric  or  Wolffian  ridge.  It  reaches  the  height  of  its  develop- 
ment in  the  human  embryo  about  the  fifth  or  sixth  week,  at  which  time  it  ex- 
tends from  the  region  of  the  heart  to  the  pelvic  region  (Fig.  346) .  Each  organ 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


389 


is  attached  to  the  dorsal  body  wall  by  a  distinct  mesentery  which,  at  its  cephalic 
end,  also  sends  off  a  band  to  the  diaphragm — the  diaphragmatic  ligament  of 
the  mesonephros.  The  peritoneum  is  reflected  over  the  surface  of  the  meso- 
nephros,  and  on  the  ventro-medial  side  the  mesothelium  becomes  thickened  to 
form  the  genital  ridge  (p.  404;  Figs.  314  and  346).  The  mesonephric  ducts  are 
embedded  in  the  lateral  parts  of  the  organs  and  extend  throughout  practically 
their  entire  length.  Since  the  ducts  are  identical  with  the  pronephric  ducts, 
they  open  at  first  into  the  caudal  end  of  the  gut,  or  cloaca  (p.  385;  Fig.  360). 
At  a  little  later  period,  when  the  urogenital  sinus  is  formed,  they  open  at  the 
junction  of  the  latter  with  the  bladder  (Fig.  363).  Still  later  they  open  into  the 


Appendage  t  * 
oftes  ' 


Testicle 


Appendage  of  epididymis 


Mesonephric  duct 
'(duct  of  epididymis) 


—  -Paradidymis 


._  Aberrant  ductule 


_  Mullerian  duct 


_     Urogenital  sinus 


FIG.  347. — Diagram  representing  certain  persistent  portions  of  the  mesonephros 
in  the  male  (see  table).     Kollmann. 

sinus  itself  (p.  400) .  A  description  of  their  further  development  is  best  deferred 
to  the  section  on  the  male  genital  organs,  since  they  become  the  genital  ducts 
(p.  416). 

The  mesonephroi  function  as  urinary  organs  during  the  period  of  their 
existence  in  the  embryos  of  all  higher  Vertebrates.  Excretory  products  are  con- 
veyed directly  to  the  tubules  by  means  of  the  glomeruli  instead  of  being  de- 
posited in  the  ccelom  and  then  taken  up  by  the  tubules,  as  is  the  case  in  func- 
tional pronephroi  (p.  386).  The  main  excretory  ducts  are  the  same  as  in  the 
pronephroi.  Aside  from  the  vessels  in  the  glomeruli  the  mesonephroi  are  ex- 
ceedingly vascular  organs.  Large  and  small  branches  of  the  posterior  cardinal 
veins  ramify  among  the  tubules  (Figs.  314  and  232).  The  blood  undergoes 


390 


TEXT-BOOK  OF  EMBRYOLOGY. 


purifying  processes  in  its  close  contact  with  the  tubules  and  is  returned  to  the 
heart  by  the  posterior  cardinals,  or,  after  the  cephalic  ends  of  the  latter  atrophy, 
by  the  subcardinals  and  the  inferior  vena  cava  (see  p.  256;  also  Fig.  232,  B). 
There  is  thus  present  a  true  renal  portal  system,  similar  to  the  hepatic  portal 
system. 

Although  the  mesonephroi  become  large  functional  organs  during  the  earlier 
stages  of  development,  they  atrophy  and  disappear  for  the  most  part,  coinci- 
dently  with  the  appearance  and  development  of  the  kidneys.  The  degeneration 
begins  during  the  sixth  or  seventh  week  and  goes  on  rapidly  until,  by  the  end  of 
the  fourth  month,  little  remains  but  the  ducts  and  a  few  tubules.  The  degenera- 


o.  t.  a. 


Ovd. 


Epo.  1. 


Epo.  t. 


FIG.  348. — Diagram  representing  certain  persistent  portions  of  the  mesonephros 

in  the  female  (see  table). 

Epo.  /.,  Longitudinal  duct  of  the  epoophoron;  Epo.  t.,  transverse  ductules  of  the  epoophoron;  O.  /.  a., 
ostium  abdominale  tubse;  Ovd.,  oviduct;  X  represents  a  small  duct  which,  if  present,  leads 
from  the  epoophoron  to  one  of  the  fimbriae  of  the  oviduct. 

tive  processes  consist  of  (i)  an  ingrowth  of  connective  tissue  among  the  tubules, 
(2)  atrophy  of  the  epithelium  of  the  tubules,  and  (3)  atrophy  of  the  glomeruli. 
The  portions  which  remain  differ  in  the  two  sexes,  and  since  the  remnants 
are  taken  up  in  the  formation  of  the  male  and  female  genital  organs  it  seems 
best  to  discuss  them  more  fully  under  those  heads  (pp.  413, 416).  The  accom- 
panying table,  however,  will  give  a  clue  to  their  fate  (see  also  Figs.  347  and 
348).  A  more  comprehensive  table  will  be  found  on  p.  423. 

Male  Female 


Mesonephros 


f  Cephalic  part 


Caudal  part 


Duct  of  mesonephros 


Efferent      ductules 
(vasa  efferentia) 

Paradidymis 
|  Vasa  aberrantia 
f  Deferent  duct 
I  Ejaculatory  duct 
[  Seminal  vesicles 


Epoophoron 


Paroophoron 


Gartner's  canals 


The  significance  of  the  mesonephroi,  which,  as  well  as  the  pronephroi,  are  present  in  the 
embryos  of  ail  higher  Vertebrates,  can  be  understood  only  by  referring  to  the  conditions  in  the 
lower  Vertebrates.  In  the  majority  of  the  Fishes  and  in  the  Amphibia  the  mesonephroi  con- 
stitute the  functional  urinary  organs  of  the  adult  and  possess  essentially  the  same  structure  as 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  391 

in  the  embryos  of  higher  forms.  Beginning  in  the  Reptiles  and  continuing  up  through  the 
series  of  Birds  and  Mammals,  another  set  of  urinary  organs — the  kidneys — develops.  The 
meson ephroi  also  develop  in  these  forms,  even  to  a  high  degree,  thus  repeating  the  ancestral 
history,  but  retain  their  original  function  only  in  the  earlier  embryonic  stages. 

THE  KIDNEY  (METANEPHROS). 

The  kidneys  are  the  third  set  of  urinary  organs  to  develop.  They  assume 
the  function  of  the  mesonephroi  as  the  latter  atrophy,  and  constitute  the  per- 
manent urinary  apparatus.  Each  kidney  is  derived  from  two  separate  anlagen 
which  unite  secondarily.  The  epithelium  of  the  ureter,  renal  pelvis,  and 
straight  renal  tubules  (collecting  tubules)  is  derived  from  the  mesonephric  duct 


Mesonephros 


Mesonephric  duct 

^^L.  ^  "  ^I's^          / 

Metanephric  blastema 


Metanephric  blastema 
(inner  zone) 

Primitive  renal  pelvis 


Cloacal  membrane -^£&  Urete 


FIG.  349. — From  a  reconstruction  of  the  anlage  of  the  kidney  (metanephros) ,  etc.,  of  a  human 
embryo  at  the  beginning  of  the  5th  week.     Schreiner. 

by  a  process  of  evagination.  The  convoluted  renal  tubules  and  glomeruli  are 
derived  directly  from  the  mesenchyme,  and  in  this  respect  resemble  the  meso- 
nephric tubules  and  glomeruli. 

The  Ureter,  Renal  Pelvis  and  Straight  Renal  Tubules.— During  the 
fourth  week  (in  embryos  of  about  5  mm.)  a  small,  hollow,  bud-like  evagination 
appears  on  the  dorsal  side  of  each  mesonephric  duct  near  its  opening  into  the 
cloaca.  The  evagination  continues  to  grow  dorsally  in  the  mesenchyme 
toward  the  vertebral  column,  and  at  the  same  time  becomes  differentiated 
into  two  parts,  a  narrow  stalk  and  a  dilated  terminal  portion.  The  stalk  is 
the  forerunner  of  the  ureter,  the  dilated  end  is  the  primitive  renal  pelvis  (Figs. 
349  and  351).  When  the  dilated  end  reaches  the  ventral  side  of  the  vertebral 


392 


TEXT-BOOK  OF  EMBRYOLOGY. 


column  it  turns  and  grows  cranially  between  the  latter  and  the  mesonephros. 
The  stalk  (or  ureter)  elongates  accordingly  (Fig.  350). 

About  the  fifth  week,  four  evaginations  from  the  primitive  renal  pelvis  appear 
— one  cephalic,  one  caudal  and  two  central  (Figs.  350  and  352).  These  may  be 
considered  as  straight  renal  tubules  of  the  first  order.  The  distal  end  of  each 
then  enlarges  to  form  a  sort  of  ampulla,  and  from  each  ampulla  two  other 
evaginations  develop,  forming  tubules  of  the  second  order.  From  the  ampulla 
of  each  secondary  tubule  two  tertiary  tubules  grow  out;  and  this  process  con- 


Mesonephros 


Mesonephric  duct 


Junction  of  meson, 
duct  and  ureter 


Cephalic  e  vagi  nation 

.Metanephric  blastema 
Central  evaginations 


Caudal  evagination 


FIG.  350. — From  a  reconstruction  of  the  anlage  of  the  kidney,  etc.,  of  a  human 
embryo  of  11.5  mm.     Schreiner. 

tinues  in  a  similar  manner  until  twelve  or  thirteen  divisions  occur,  the  final 
divisions  occurring  during  the  fifth  month.  The  tubules  grow  into  the  mesen- 
chyme  which  surrounds  the  pelvis  and  which  forms  the  so-called  metanephric 
blastema,  or  nephro genie  tissue  (Fig.  351). 

If  the  straight  tubules  were  to  remain  in  this  condition,  only  four  would  open 
directly  into  the  pelvis,  corresponding  with  the  four  primary  evaginations.  In 
the  adult,  however,  many  hundreds  open  into  the  pelvis;  consequently  extensive 
changes  of  the  early  condition  must  take  place.  These  changes  are  similar  to 


THE  DEVELOPMENT  OF  THE  UROGEXITAL  SYSTEM. 


393 


the  process  by  which  the  proximal  ends  of  some  of  the  blood  vessels  come  to  be 
included  in  the  wall  of  the  heart  (p.  235).  The  proximal  ends  of  the  tubules 
become  wider,  the  pelvis  swells  out,  and  the  walls  of  the  tubules  become  in- 
cluded in  the  wall  of  the  pelvis.  In  certain  parts  of  the  pelvic  wall  this  process 
goes  on  until  deep  bays — the  calyces — are  formed,  into  which  a  large  number  of 
tubules  open.  In  the  other  parts  of  the  wall  the  process  does  not  go  so  far,  thus 
leaving  promontories — the  renal  papilla — upon  which  larger  tubules  or  papil- 
lary ducts  open.  The  adult  renal  pelvis  thus  consists  of  the  primitive  pelvis  plus 
the  proximal  ends  of  the  straight  tubules. 


Metanephric  I 
blastema  | 


Primitive 
renal  pelvis 


Ureter 

Mesonephric  duct 
Intestine 

.    Bladder 


FIG.  351. — From  a  transverse  section  of  a  human  embryo  at  the  beginning  of  the  5th  week. 
The  plane  of  the  section  is  indicated  in  Fig.  349.     Schreiner. 


The  Convoluted  Renal  Tubules  and  Glomeruli. — As  stated  above, 
the  metanephric  blastema  or  nephrogenic  tissue  surrounds  the  renal  pelvis 
and  the  straight  tubules.  It  represents  a  condensation  of  the  mesenchyme  and  is 
destined  to  give  rise  to  the  convoluted  tubules  and  glomeruli.  The  cells  of  the 
blastema  in  the  region  of  the  ampullae  of  the  terminal  straight  tubules  acquire 
an  epithelial  character  and  become  arranged  in  solid  masses  (Fig.  353).  Each 
mass  unites  with  an  ampulla  and  acquires  a  lumen,  which  becomes  continuous 
with  the  lumen  of  the  straight  tubule,  then  elongates  and  forms  an  S-shaped 
structure  (Figs.  354  and  355).  The  loop  of  the  S  nearer  the  straight  tubules 
elongates  still  more  and  grows  toward  the  pelvis,  parallel  with  the  straight 


394  TEXT-BOOK  OF  EMBRYOLOGY. 

tubules,  to  form  Henle's  loop.  The  part  between  Henle's  loop  and  the  straight 
tubule  elongates  and  becomes  convoluted  to  form  the  proximal  part  of  a  con- 
voluted renal  tubule  (second  convoluted  tubule).  The  part  between  the  distal 
end  and  Henle's  loop  elongates  and  becomes  convoluted  to  form  the  distal  part 
of  a  convoluted  renal  tubule  (first  convoluted  tubule)  (Figs.  356  and  357). 

To  avoid  confusion  it  may  be  well  to  call  attention  to  the  fact  that  what  has  here  been 
called  the  proximal  part  of  a  convoluted  tubule  corresponds  with  what  is  usually  described  as 
the  second  or  distal  convoluted  tubule,  and  that  the  distal  part  of  a  convoluted  tubule 
corresponds  with  the  first  or  proximal  convoluted  tubule.  In  histology  the  distal  and  proxi- 
mal convoluted  tubules  are  spoken  of  in  relation  to  the  renal  corpuscle,  but  in  development 
it  is  more  convenient  to  speak  of  the  terminal  part  of  a  tubule  as  its  distal  part. 


Cephalic 
evagination 


Caudal 
evagination 


Ureter 


FIG.  352. — From  a  model  of  the  primitive  renal  pelvis  and  the  evaginations  which  form  the  cephalic, 
central  and  caudal  straight  renal  tubules  of  the  first  order.  Human  embryo  of  4!  months. 
Compare  with  Fig.  350.  Schreiner 

A  glomerulus  develops  in  connection  with  the  extreme  distal  end  of  a  con- 
voluted tubule  or,  in  other  words,  with  the  distal  loop  of  the  S  (p.  393).  There 
occurs  here  a  further  condensation  of  the  mesenchyme,  into  which  grows  a 
branch  from  the  renal  artery.  This,  as  the  afferent  vessel  of  the  glomerulus, 
breaks  up  into  several  arterioles,  each  of  which  gives  rise  to  a  tuft  of  capillaries. 
These  tufts  are  separated  from  one  another  by  somewhat  more  mesenchymal 
tissue  than  separates  the  capillaries  within  a  tuft.  The  tufts  with  the  asso- 
ciated mesenchymal  tissue  constitute  a  glomerulus,  and  it  is  the  mesenchymal 
septa  between  the  tufts  that  give  to  the  glomerulus  its  characteristic  tabulated 
appearance.  The  capillaries  of  each  tuft  empty  into  an  arteriole,  and  the 
several  arterioles  unite  to  form  the  efferent  vessel  of  the  glomerulus,  which  passes 
out  along  side  of  the  afferent  vessel.  The  renal  tubule  becomes  flattened  on  the 
side  next  the  condensation  of  the  mesenchyme,  and  as  the  glomerulus  develops, 
the  epithelium  of  the  tubule  grows  around  it  except  at  the  point  where  the  blood 

\ 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


395 


vessels  enter  and  leave.  Thus  a  double  layer  of  epithelium  comes  to  surround 
the  glomerulus,  the  space  between  the  two  layers  being  the  extreme  distal  part 
of  the  lumen  of  a  renal  tubule.  The  inner  layer  is  closely  applied  to  the  surface 


I   Anlagen  of 
>  convoluted 
renal  tubules 


Renal  pelvis 


Capsule 


Anlage  of 

convoluted  renal  tubule 

Ampulla  of 
straight  renal  tubule 


FIG.  353. — Sagittal  section  of  the  anlage  of  the  left  kidney  in  a  rabbit  embryo  of  15  days.  Schreiner. 
The  straight  renal  tubules  (sections  of  which  are  shown)  are  embedded  in  the  metanephric  blastema. 

Condensations  of  the  latter  form  the  anlagen  of  the  convoluted  renal  tubules.     At  the  left 

of  the  figure  several  mesonephric  tubules  are  shown. 


Amp. 


Con.  r.  t. 


Met.  bl. 


Con.  r.  t. 


FIG.  354. — From  a  section  of  the  kidney  of  a  human  foetus  of  7  months.     Schreiner. 

Amp.,  Ampulla  of  a  straight  renal  tubule;  Con.  r.  /.,  anlagen  of  convoluted  renal  tubules,  above  and 

between  which  are  two  ampullae  (compare  Fig.  355);  met.  bl.,  metanephric  blastema. 

of  the  glomerulus  and  even  dips  down  into  the  latter  between  the  tufts.  The 
outer  layer  forms  Bowman's  capsule,  the  flat  epithelium  of  which  passes  over 
into  the  cuboidal  epithelium  of  the  "neck"  of  the  tubule,  and  this  in  turn  is 


396 


TEXT-BOOK  OF  EMBRYOLOGY. 


Pros,  convoluted  tubule 
Dist.  convoluted  tubul 
Henle's  loo 


FIG.  355- 


Ampulla  of  straight  tubule 


Henle's  loop 

Distal  part  of 
convoluted  tubule 


Bowman's  capsule 


Proximal  part  of 
convoluted  tubule 


Distal  part  of 
convoluted  tubule 


"Neck" 
Bowman's  capsule 


FIG.  356. 


Prox.  convoluted  tubule 
Dist.  convoluted  tubule 
Henle's  loop 


Prox.  convoluted  tubule^ 
Bowman's  capsule 
Straight  tubule 


Prox.  convoluted  tubule 
Dist.  convoluted  tubule 

Prox.  convoluted  tubule 


Dist.  convoluted  tubule 
—    Bowman's  capsule 

Ascending     } 

>  arm  of  Henle's  loop 
Descending  J 


FIG.  357. 

F;GS-  355>  356  and  357-— From  reconstructions  of  convoluted  renal  tubules  in  successive 
stages  of  development.     Stoerk. 


THE  DEVELOPMENT  OF  THE  UROGEXITAL  SYSTEM.  397 

continuous  with  the  pyramidal  epithelium  of  the  distal  convoluted  tubule. 
The  entire  structure  is  a  renal  corpuscle.  The  formation  of  renal  corpuscles 
begins  in  embryos  of  30  mm.  and  continues  until  after  birth. 

The  Renal  Pyramids  and  Renal  Columns. — The  tubules  arising  from 
the  four  primary  evaginations  of  the  renal  pelvis  together  form  four  distinct 
groups  or  primary  renal  (Malpighian)  pyramids — one  cephalic,  one  caudal,  and 
two  central.  The  central  pyramids  are  crowded  in  between  the  end  pyramids, 
(cephalic  and  caudal)  and  do  not  develop  as  rapidly  as  the  latter  which  soon 
bend  around  toward  the  ureter,  thus  resulting  in  the  formation  of  the  convex 
side  of  the  kidney  and  a  depression  or  hilus  opposite  (compare  Figs.  352  and 
358) .  Between  these  four  pyramids  the  mesenchyme  remains  for  some  time  as 

Primary  renal  pyramid 


'Primary  renal  column 
Cephalic  straight  tubule- 
Primary  renal  pyramid 
Central  straight  tubule =•— 

___^^^^^_^^_^^^^_          Primary  renal  column 
Caudal  straight  tubule 


Urett 

Primary  renal  pyramid 
FIG.  358. — Frontal  section  of  the  kidney  of  a  human  foetus  of  3!  months  (10  cm.).     Hauch. 

rather  distinct  septa,  forming  the  primary  renal  columns  (columns  of  Bertini) 
which  are  marked  by  corresponding  depressions  on  the  surface  of  the  kidney 
and  extend  to  the  renal  pelvis.  The  four  primary  pyramids  may  be  considered 
as  lobes  (Fig.  358).  It  should  also  be  stated  that  the  parts  of  the  tubules 
derived  from  the  mesenchyme  form  the  bases  of  the  renal  pyramids.  Be- 
tween the  groups  of  straight  tubules  derived  from  evaginations  of  the  second  or 
third  order  (see  p.  392)  there  are  also  septa  of  mesenchyme  which  divide  each 
primary  pyramid  into  two  or  three  secondary  pyramids.  These  septa  may 
be  considered  as  secondary  renal  columns  (Fig.  359).  Thus  the  entire  kidney 
is  divided  into  from  eight  to  twelve  secondary  pyramids.  Tertiary  renal 
columns  then  divide  incompletely  the  secondary  pyramids  into  tertiary  pyra- 


398 


TEXT-BOOK  OF  EMBRYOLOGY. 


mids.     These  are  apparent  on  the  surface  of  the  kidney  and  constitute  the 
surface  tabulation,  but  are  not  clearly  denned  in  the  interior. 

The  formation  of  renal  papillae  (p.  393)  corresponds  to  the  formation  of 
pyramids  only  to  a  certain  point,  for  some  of  the  tertiary  pyramids  appear  only 
near  the  surface  and  consequently  do  not  have  corresponding  papillae.  This 
accounts  for  the  fact  that  frequently  the  number  of  pyramids  apparent  on  the 
surface  does  not  correspond  with  the  number  of  papillae.  The  surface  lobula- 
tion  is  very  plainly  marked  in  kidneys  up  to  and  for  a  short  time  after  birth.  It 
then  disappears  and  the  surface  becomes  smooth.  At  the  same  time  the  con- 
nective (mesenchymal)  tissue  of  the  renal  columns  is  largely  replaced  by  the 

Secondary 

renal 
column    Secondary 

renal 

pyramid       Secondary 
renal 
column 


FIG.  359. — Frontal  section  of  the  kidney  of  a  human  foetus  of  19  weeks  (17.5  cm.).     Hauch. 

epithelial  elements  of  the  gland  so  that  in  the  adult  kidney  the  columns  are  not 
clearly  denned. 

The  capsule  of  the  kidney  is  derived  from  the  mesenchyme  which  surrounds 
the  anlage  of  the  organ  (Fig.  353) .  This  mesenchyme  is  transformed  into  fibrous 
connective  tissue  and  a  small  amount  of  smooth  muscle,  forming  a  layer  which 
closely  invests  the  kidney  and  dips  into  the  hilus  where  it  surrounds  the  blood 
vessels  and  the  end  of  the  ureter.  The  connective  tissue  and  muscle  of  the 
ureter  are  also  derived  from  the  mesenchyme. 

CORTEX  AND  MEDULLA. — As  the  convoluted  renal  tubules  develop  in  the 
metanephric  blastema  (p.  393),  they  form  a  cap-like  mass  around  the  group  of 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  399 

straight  tubules.  This  is  the  beginning  of  the  renal  cortex.  A  true  cortex, 
however,  can  be  spoken  of  only  after  the  appearance  of  the  glomeruli  (in 
embryos  of  30  mm.).  Its  peripheral  boundary  is  the  capsule,  and  the  renal 
corpuscles  nearest  the  pelvis  mark  its  inner  boundary.  The  mass  of  straight 
tubules  forms  the  bulk  of  the  medulla.  It  does  not  at  this  stage  contain  Henle's 
loops,  the  latter  developing  later  (during  the  fourth  month).  Both  cortex 
and  medulla  increase  until  the  kidney  reaches  its  adult  size.  The  cortex 
increases  relatively  faster  than  the  medulla  up  to  the  seventh  year;  after 
this  the  increase  is  practically  equal.  The  medullary  rays  are  probably 
secondary  formations,  being  formed  by  groups  of  straight  tubules  which 
grow  out  into  the  cortex;  later,  ascending  arms  of  Henle's  loops  are  added  to 
these  groups. 

Some  of  the  glomeruli  of  the  first  generation  are  much  larger  than  any 
found  in  the  adult.  In  some  of  the  lower  Mammals  these  "giant"  glomeruli 
disappear  and  it  is  probable  that  the  same  occurs  in  the  human  embryo.  Some 
of  the  tubules  also  degenerate  and  disappear.  The  cause  of  these  phenomena 
is  not  known. 

Changes  in  the  Position  of  the  Kidneys.— As  has  already  been  described 
(p.  391),  the  kidney  buds  first  grow  dorsally  from  the  mesonephric  ducts 
toward  the  vertebral  column.  They  then  grow  cranially,  with  a  corresponding 
elongation  of  the  ureters,  and  in  embryos  of  20  mm.  they  lie  for  the  most  part 
cranial  to  the  common  iliac  arteries.  This  migration  continues  until  the  time 
of  birth  when  the  cephalic  ends  of  both  kidneys  reach  the  eleventh  thoracic  ver- 
tebra. When  the  kidneys  begin  to  move  cranially  the  hilus  is  directed  caudally. 
Later  they  rotate  and  the  hilus  is  turned  toward  the  medial  sagittal  plane. 

Since  the  ureter,  renal  pelvis  and  straight  tubules  develop  from  the  mesonephric  ducts, 
and  since  the  convoluted  tubules  and  glomeruli  develop  directly  from  the  same  tissue  as  the 
mesonephric  tubules,  namely,  the  mesenchyme,  the  renal  tubules  may  be  said  to  represent 
the  third  generation  of  urinary  tubules.  But  no  definite  reason  for  the  appearance  of  the 
third  generation  can  be  given.  The  atrophy  of  the  mesonephroi  would,  of  course,  make 
necessary  the  compensatory  development  of  new  structures;  but  this  only  carries  the  problem 
a  step  further  back,  for  the  cause  of  the  atrophy  of  the  mesonephroi  is  not  clear.  In  regard 
to  this  atrophy,  however,  there  is  a  suggestion  of  a  cause  in  the  fact  that  in  the  Amphibia 
the  mesonephroi  are  in  part  used  for  conveying  the  sexual  elements,  which  leaves  the  meso- 
nephroi less  free  to  function  as  urinary  organs.  Possibly  the  loss  of  freedom  to  function  leads 
to  the  development  of  new  structures — the  kidneys — in  the  higher  forms  (Reptiles,  Birds 
and  Mammals).  In  these  forms  the  kidneys  assume  the  urinary  function  after  the  early 
embryonic  stages,  and  only  the  ducts  and  a  part  of  the  tubules  of  the  mesonephroi  persist  in 
the  male  to  convey  the  sexual  elements.  Thus  the  persistent  parts  of  the  mesonephroi  as- 
sume a  new  function  as  the  old  one  is  lost.  But,  on  the  other  hand,  complications  arise 
on  account  of  the  fact  that  in  the  female  the  sexual  products  are  carried  off  by  another  set 
of  ducts  (the  Mullerian  ducts),  which  develop  in  both  sexes  but  disappear  in  the  male, 
while  the  mesonephroi  and  their  ducts  disappear  almost  entirely. 


400 


TEXT-BOOK  OF  EMBRYOLOGY. 


THE  URINARY  BLADDER,  URETHRA  AND  UROGENITAL  SINUS. 

As  described  elsewhere,  the  allantois  appears  at  an  early  stage  as  an  evagi- 
nation  from  the  ventral  side  of  the  caudal  end  of  the  primitive  gut  (Fig.  282), 
grows  out  into  the  belly  stalk,  and  finally  becomes  enclosed  in  the  umbilical  cord 
(p.  114).  As  the  embryo  develops,  the  proximal  end  of  the  allantois  becomes 
elongated  to  form  a  stalk  or  duct  which  extends  from  the  caudal  end  of  the 
gut  to  the  umbilicus  (Fig.  285).  The  portion  of  the  gut  immediately  caudal  to 
the  attachment  of  the  allantoic  duct  becomes  dilated  to  form  the  cloaca  which 
at  first  is  a  blind  sac,  its  cavity  being  separated  from  the  outer  surface  of  the 
embryo  by  the  cloacal  membrane  (Fig.  360) .  The  latter  is  composed  of  a  layer  of 
entoderm  and  a  layer  of  ectoderm,  with  a  thin  layer  of  mesoderm  between.  The 
cloaca  then  becomes  separated  into  two  parts— a  larger  ventral  part  which  forms 


Intestine        Kidney  bud 


Mesonephric  duct 

Urachus 

Cloaca 

Cloacal  membrane 


Caudal  gut  — — 

Notochord \ 

Neural  tube 

FIG.  360. — From  a  model  of  the  cloaca  and  the  surrounding  structures  in  a 
human  embryo  of  6.5  mm.     Keibel. 

the  urogenital  sinus  and  a  smaller  dorsal  part  which  forms  the  rectum.  This 
is  accomplished  by  a  fold  or  ridge  which  grows  from  the  lateral  wall  into  the 
lumen  and  meets  and  fuses  with  its  fellow  of  the  opposite  side.  The  fusion  be- 
gins at  the  cephalic  end,  in  the  angle  between  the  allantoic  duct  and  the  gut, 
and  gradually  proceeds  caudally  until  the  separation  is  complete  as  far  as  the 
cloacal  membrane.  The  mass  of  tissue  forming  the  partition  is  called  the  uro- 
rectaljold,  (Fig.  361) .  The  openings  of  the  mesonephric  ducts,  which  primarily 
were  situated  in  the  lateral  cloacal  wall  (p.  389),  are  situated  after  the  separation 
in  the  dorso-lateral  wall  of  the  urogenital  sinus  (compare  Figs.  360,  361,  362). 
During  the  separation  of  the  urogenital  sinus  from  the  rectum,  certain 
changes  take  place  in  the  proximal  ends  of  the  mesonephric  ducts  and  ureters. 
The  ends  of  the  ducts  become  dilated  and  are  gradually  taken  up  into  the  wall  of 
the  sinus.  This  process  of  absorption  continues  until  the  ends  of  the  ureters  are 
included,  with  the  result  that  the  ducts  and  ureters  open  separately,  the  latter 


THE  DEVELOPMENT  OF  THE  UROGEXITAL  SYSTEM.  401 

slightly  cranial  and  lateral  to  the  former.  (Compare  Figs.  362  and  363.)  This 
condition  is  reached  in  embryos  of  12  to  14  mm.  The  point  at  which  these  two 
sets  of  ducts  open  marks  the  boundary  between  a  slightly  larger  cephalic  part 
of  the  sinus,  the  anlage  of  the  bladder,  and  a  smaller  caudal  part  which  becomes 
the  urethra  and  urogenital  sinus  (Fig.  363). 

After  the  second  month  the  bladder  becomes  larger  and  more  sac-like,  and 
the  openings  of  the  ureters  migrate  farther  cranially  to  their  final  position.  The 
lumen  of  the  bladder  is  at  first  continuous  with  the  lumen  of  the  allantoic  duct, 
but  the  duct  degenerates  into  a  solid  cord  of  cells,  the  urachus.  The  latter 
degenerates  still  further  and  finally  remains  only  as  the  middle  umbilical  liga- 

Urorectal  fold  Mesonephric  duct 

^^^  ^^^^         Kidney  bud. 

Urachus 


Cloaca 
Urogenital  sinus 


Cloacal  membrane  ~  * — • Rectum 


audal  gut 


FIG.  361. — From  a  model  of  the  cloacal  region  of  a  human  embryo  slightly  older  than 

that  shown  in  Fig.  360.     Keibel. 

The  arrow  points  to  the  developing  partition  (urorectal  fold)  between  the  rectum  and  urogenital 
sinus.  The  opening  of  the  mesonephric  duct  into  the  urogenital  sinus  is  indicated  by  a 
small  seeker. 

ment.  It  seems  quite  probable  that  the  bladder  is  derived  almost  wholly  from 
the  cloaca.  A  small  part  arises  from  the  inclusion  of  the  ends  of  the  mesoneph- 
ric ducts.  If  any  part  is  derived  from  the  allantoic  duct,  it  is  only  the  apex. 
After  the  bladder  begins  to  enlarge,  the  adjacent  portion  of  the  urogenital 
sinus  becomes  slightly  constricted.  This  marks  the  beginning  of  the  urethra. 
In  the  female  the  constricted  part  represents  practically  the  entire  urethra. 
In  the  male  it  represents  only  the  proximal  end,  the  other  portion  developing 
in  connection  with  the  penis  (p.  428).  The  urogenital  sinus  is  narrow  and 
tubular  at  its  junction  with  the  urethra;  more  distally  it  is  wider  and  is  shut  off 
from  the  exterior  by  the  cloacal  membrane.  After  the  embryo  reaches  a  length 
of  1 6  to  17  mm.,  the  membrane  ruptures  and  the  sinus  opens  on  the  surface. 


402 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  narrow  part  of  the  sinus  is  gradually  taken  up  into  the  wider,  resulting  in 
the  formation  of  a  sort  of  vestibule.  In  both  sexes  the  urethra  opens  into  the 
deeper  end  of  the  vestibule.  In  the  male  the  mesonephric  (seminiferous) 


Cloaca 
(undivided  portion) 


Cloacal  membrane 


Tail 


Mesonephric  ducts 
Ccelom 


—  Primitive  renal  pelvis 


Rectum 


FIG.  362. — From  a  reconstruction  of  the  caudal  end  of  a  human  embryo 
of  11.5  mm.  (4^  weeks).     Keibel. 


Umbilical  artery 
Bladder 


Symphysis  pubis 
Urogenital  si 


Genital  tubercle 
Urethra 


Ovary 

Broad  ligament 
of  uterus 


-  Mullerian  duct 

•  Mesonephric  duct 
Ureter 


Recto-uterine 
excavation 


Rectum 


Tail 


FIG.  363. — From  a  reconstruction  of  the  caudal  end  of  a  human  embryo 

of  25  mm.  (8^-9  weeks).     Keibel. 
The  asterisk  (*)  indicates  the  urorectal  fold. 

ducts  open  near  the  external  orifice.     In  the  female  the  opening  of  the  develop- 
ing vagina  is  situated  on  the  dorsal  side  near  the  external  orifice. 

The  epithelium  of  the  prostate  gland  is  derived  by  evagination  from  the  proxi- 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  403 

mal  part  of  the  urethra.  The  first  evagination  appears  during  the  third  month. 
In  the  male  the  process  continues  to  form  a  rather  large  gland;  in  the  female  the 
structure  remains  in  a  rudimentary  condition.  During  the  fourth  month  two 
evaginations  arise  from  the  urethra  and  develop  into  the  bulbo-urethral 
(Cowper's)  glands  in  the  male,  into  the  larger  vestibular  (Bartholin's)  glands  in 
the  female. 

From  the  course  of  development  it  is  seen  that  the  epithelium  of  most  of  the 
bladder,  of  the  female  urethra  and  proximal  end  of  the  male  urethra,  of  the 


Germinal  j|a  •.  Stroma 

epithelium  — t  mm       (mesenchyme) 

(mesothelium) 


FIG.  364. — Transverse  section  through  the  germinal  epithelium  of  a  pig  embryo  of  n  mm.    Nagel. 

The  larger  cells  in  the  epithelium  represent  the  sex  cells,  the  smaller  ones  the 

undifferentiated  mesothelial  cells. 

prostate,  of  the  urogenital  sinus,  and  of  the  bulbo-urethral  and  vestibular 
glands  is  of  entodermal  origin.  A  very  small  part  of  the  bladder  epithelium 
is  of  mesodermal  origin,  since  the  proximal  ends  of  the  mesonephric  ducts, 
which  are  mesodermal  derivatives,  are  taken  up  into  the  wall.  All  the  connec- 
tive tissue  and  smooth  muscle  associated  with  these  organs  are  derived  from 
the  mesoderm  (mesenchyme)  which  surrounds  the  anlagen. 

THE  GENITAL  GLANDS. 
The  Germinal  Epithelium  and  Genital  Ridge. 

At  a  very  early  stage  in  the  formation  of  the  mesonephros,  a  narrow  strip 
of  mesothelium  extending  along  the  medial  surface  becomes  thicker  and  the 
cells  become  arranged  in  several  layers  (Figs.  314  and  346).  The  cells  become 
differentiated  into  two  kinds — (i)  small  cuboidal  cells  with  cytoplasm  which 
stains  rather  intensely,  and  (2)  larger  spherical  cells  with  clearer  cytoplasm  and 


404  TEXT-BOOK  OF  EMBRYOLOGY. 

large  vesicular  nuclei  (Fig.  364).  The  latter  are  the  sex  cells;  and  the  whole 
epithelial  (mesothelial)  band  is  known  as  the  germinal  epithelium.  The  sex 
cells  are  destined  to  give  rise  to  the  sexual  elements — in  the  female  to  the  ova, 
in  the  male  to  the  spermatozoa.  In  the  earlier  stages,  however,  it  is  impossible 
to  determine  whether  the  sex  cells  will  give  rise  to  male  or  female  elements. 
The  differentiation  of  sex  and  the  corresponding  histological  differentiation  of 
the  sex  cells  occur  at  a  later  period. 

In  his  recent  work  on  the  ovary  and  testis  in  Mammals,  Allen  has  ob- 
served in  very  early  stages  (pig  embryos  of  6  mm.,  rabbit  embryos  of  13  days) 
certain  large  cells,  with  large  clear  nuclei,  in  the  mesenchymal  tissue  of  the 
mesentery,  outside  of  the  genital  ridge.  These,  from  their  resemblance  to  the 
sex  cells  within  the  genital  ridge,  should  probably  also  be  classed  as  sex  cells. 
Their  origin  in  these  animals,  however,  is  not  known  with  certainty;  but 
the  fact  that  in  turtle  embryos  Allen  has  found  cells  of  a  similar  character 
apparently  migrating  from  the  entoderm  through  the  mesoderm  to  the  site  of 
the  genital  glands  suggests  the  possibility  that  they  are  entodermal  derivatives. 
It  is  doubtful  whether  these  aberrant  sex  cells  take  part  in  the  development  of 
the  mature  sexual  elements,  the  latter  in  all  probability  being  derived  from 
the  sex  cells  of  the  mesothelium  of  the  genital  ridge. 

Beard,  Eigenmann,  Rabl,  Woods,  and  others,  have  described  sex  cells,  undoubtedly 
homologous  with  the  aberrant  sex  cells  mentioned  above,  as  occurring  in  various  regions  of 
the  embryos  of  certain  Fishes.  These  investigators  also  assert  that  the  sex  cells  become 
specialized  and,  so  to  speak,  segregated  at  a  very  early  period  of  development,  even  at  the 
stage  of  blastomere  formation.  Beard  contends  that  the  early  differentiated  sex  (or  germ) 
cells  are  significant  in  the  origin  of  certain  teratomata  (see  Chapter  on  Teratogenesis). 

The  cells  of  the  germinal  epithelium  increase  in  number  by  mitotic  division 
and,  for  some  time  at  least,  the  sex  cells  continue  to  increase  in  number  by 
differentiation  from  the  small  cuboidal  (indifferent)  cells,  as  indicated  by  the 
presence  of  intermediate  stages  between  the  two  types.  The  germinal  epi- 
thelium soon  becomes  separated  into  two  layers — (i)  a  superficial  layer  which 
retains  its  epithelial  character  and  contains  the  sex  cells,  and  (2)  a  deeper  layer 
composed  of  smaller  cells  which  resemble  those  of  the  mesenchyme  and  which 
give  rise  to  a  part,  at  least,  of  the  stroma  of  the  genital  glands.  The  elevation 
formed  by  these  two  layers  projects  into  the  body  cavity  from  the  medial  side 
of  the  mesonephros  and  constitutes  the  genital  ridge  (Fig.  346).  From  the 
superficial  epithelial  layer,  columns  or  cords  of  cells,  containing  some  of  the 
sex  cells,  grow  into  the  underlying  tissue.  This  ingrowth,  however,  does  not 
occur  equally  in  all  parts  of  the  genital  ridge,  for  three  fairly  distinct  regions 
can  be  recognized.  In  the  cephalic  end  comparatively  few  columns  appear, 
but  these  few  grow  far  down  into  the  underlying  tissue  and  constitute  the  rete 
cords.  In  the  middle  region  a  greater  number  of  columns  grow  into  the 


THE  DEVELOPMENT  OF  THE  UROGEXITAL  SYSTEM. 


405 


stroma,  forming  the  sex  cords.  In  the  caudal  region  there  are  practically  no 
columns.  At  first  the  line  of  demarkation  between  the  cell  columns  and  the 
stroma  is  not  clearly  defined^ 

The  changes  thus  far  described  are  common  to  both  sexes  and  are  completed 
during  the  fourth  or  fifth  week.  The  genital  ridges  or  anlagen  of  the  genital 
glands  constitute  "indifferent"  structures  which  later  become  differentiated  into 
either  ovaries  or  testicles. 


Differentiation  of  the  Genital  Glands. 

After  the  fourth  or  fifth  week,  certain  changes  occur  in  the  genital  ridges 
which  differ  accordingly  as  the  ridges  form  ovaries  or  testicles.  While  the 
differences  are  at  first  not  particularly  obvious,  there  are  four  which  become 
clearer  as  the  changes  progress,  (i)  If  the  ridge  is  to  become  a  testicle,  the 
cells  of  the  surface  epithelium  become  arranged  in  a  single  layer  and  become 


Rete  cords 
(Rete  testis) 


Mesorchium 


Mesothelium 


Tunica 
albuginea 


Mesonephros 


Sex  cords 
(convoluted  semin- 
iferous tubules) 


Glomerulus 


FIG.  365. — Transverse  section  of  the  left  testicle  of  a  pig  embryo  of  62  mm.     Bonnet. 

flat.     (2)  In  a  developing  testicle  a  layer  of  dense  connective  tissue  grows  be- 
tween the  surface  epithelium  and  the  sex  cords,  forming  the  tunica  albuginea. 

(3)  In  a  testicle  there  also  appears  a  sharper  line  of  demarkation  between  the 
cell  columns  and  the  stroma,  and  the  latter  shows  a  more  extensive  growth. 

(4)  Another  feature  of  the  testicle  is  that  the  sex  cells  begin  to  be  less  con- 
spicuous and  do  not  increase  further  in  size,  but  come  to  resemble  the  other 
epithelial  elements.     The  ovarian  characters  are  to  a  certain  extent  the  oppo- 
site,    (i)  The  surface  epithelium  does  not  become  flattened.     (2)  A  layer  of 
connective  tissue,  corresponding  to  the  albuginea  of  the  testicle,  grows  be* 


406 


TEXT-BOOK  OF  EMBRYOLOGY. 


tween  the  epithelium  and  the  deeper  parts,  but  is  of  a  looser  nature.  (3)  There 
is  a  less  sharp  line  of  demarkation  between  the  cell  columns  and  the  stroma. 
(4)  The  sex  cells  continue  to  increase  in  size  and  become  more  conspicuous. 
(Compare  Figs.  365  and  366.) 

During  these  processes  of  development,  the  anlage  of  each  genital  gland  be- 
comes more  or  less  constricted  from  the  mesonephros  and  finally  is  attached  only 
by  a  thin  sheet  of  tissue — the  mesovarium  in  the  female  or  the  mesorchium  in  the 


Oviduct 

(Ostium  abdom- 

inale  tubae) 


Cortex 


Medullary  cords 

(Medulla)  ~ 


-4 Epoophoron 


Rete  cords 
-  (Rete  ovarii) 


-Mesonephros 


Oviduct 
FIG.  366. — Longitudinal  section  of  the  ovary  of  a  cat  embryo  of  94  mm.    Semidiagrammatic.    Coert. 


male  (p.  419).     At  the  same  time  the  anlage  grows  more  rapidly  in  thickness 
than  in  length  and  assumes  an  oval  shape. 

The  Ovary. — As  stated  above,  a  layer  of  loose  connective  tissue,  correspond- 
ing to  the  albuginea  of  the  testicle,  grows  in  between  the  surface  epithelium  and 
the  cell  columns  (sex  cords)  and  effects  a  more  or  less  complete  separation. 
The  sex  cords  are  thus  pushed  farther  from  the  surface,  become  more  clearly 
marked  off  from  the  surrounding  stroma  and  constitute  the  so-called  medullary 
cords.  The  cortex  of  the  ovary  at  this  stage  is  represented  only  by  the  surface 
(germinal)  epithelium,  which  is  composed  of  several  layers  of  cells  and  contains 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  407 

numerous  sex  cells  in  various  stages  of  differentiation  (Fig.  367).  The 
rete  cords  which  arise  in  the  cranial  end  of  the  "indifferent"  gland  (p.  404) 
come  to  lie  in  what  will  be  the  hilus  of  the  ovary.  The  ovary  may  thus  be 
said  to  be  composed  of  two  parts — (i)  the  rete  anlage  and  (2)  the  stratum  ger- 
minativum.  The  latter  is  subdivided  by  the  albuginea  into  (a)  medulla  and 
(b)  cortex. 

i.  The  rete  cords  develop  into  a  group  of  anastomosing  trabeculae  which  con- 
stitute the  rete  ovarii,  situated  in  the  hilus  but  nearer  the  cephalic  end  of  the 
gland  (Fig.  366).  They  are  the  homologues  of  the  rete  testis.  The  cells  com- 
posing them  are  smaller  and  darker  than  those  of  the  medullary  cords.  Sprouts 
grow  out  from  the  rete  cords  and  unite  with  the  medullary  cords  and  the  meso- 
nephric  tubules.  (The  same  process  occurs  in  the  testicle,  where  the  rete  cords 
give  rise  to  the  functional  rete  testis  and  straight  seminiferous  tubules.)  In 


Cortex :^R«**.v,  '.'*\\  V"-  f&.f-'r'Ji^^^^m^^. Mesothelium 

(Germinal  epithelium) 


Medulla  — -i 


Mesovarium 


Rete  ovarii 


FIG.  367. — Transverse  section  of  the  ovary  of  a  fox  embryo.     Biihler  in  Hertwig's  Handbuch. 
The  large  clear  cells  are  the  primitive  ova. 

some  of  the  cords  lumina  appear  and  are  lined  with  irregular  epithelium. 
Such  a  condition  represents  the  height  of  their  development  in  the  ovary. 
From  this  time  on,  they  degenerate  and  finally  disappear.  The  time  of  their 
disappearance  varies  in  different  individuals;  they  usually  persist  until  birth, 
sometimes  until  puberty. 

Formerly  it  was  thought  that  the  rete  cords  were  derived  from  the  meso- 
nephric  tubules  and  entered  the  genital  glands  secondarily.  More  recent  re- 
searches have  demonstrated  quite  conclusively,  however,  that  they  are  deriva- 
tives of  the  germinal  epithelium  and  unite  with  the  mesonephric  tubules 
secondarily. 

2  (a).  The  medullary  cords  are  composed  of  small  epithelial  cells,  contain  a 
number  of  larger  sex  cells  or  primitive  ova,  and  are  surrounded  by  stroma 
(Figs.  367,  368).  They  are  connected  with  the  rete  cords  and  in  some  places 
with  the  germinal  epithelium.  During  foetal  life  they  give  rise  to  primary 
ovarian  (Graafian)  follicles;  later  they  degenerate  and  finally  disappear. 


408 


TEXT-BOOK  OF  EMBRYOLOGY. 


2(b).  The  cortex  of  the  ovary,  as  stated  above,  at  first  consists  of  several 
layers  of  small,  darkly  staining  cells,  among  which  are  many  large,  clearer  sex 
cells  or  primitive  ova  (Fig.  367).  From  the  epithelium,  masses  or  cords  of  cells 
grow  into  the  underlying  tissue,  carrying  with  them  some  of  the  primitive  ova. 
These  masses  are  known  as  P  finger's  egg  cords.  In  some  cases  several  ova  are 
grouped  together,  forming  egg  nests  (Fig.  368).  The  epithelial  cells  are  the 
progenitors  of  the  follicular  cells  and  constantly  undergo  mitotic  division.  The 
primitive  ova,  on  the  other  hand,  increase  in  size  and  their  nuclei  show  distinct 
intranuclear  networks. 

The  egg  cords  become  separated  from  the  surface  epithelium  and  are 
broken  up  so  that  in  most  cases  a  single  ovum  is  surrounded  by  a  single  layer  of 


Germinal 
epithelium 


Cortex 


Medulla 


FIG.  368. — From  a  section  through  the  ovary  of  a  human  foetus  of  4  months.    Meyer-Ruegg,  Btih/er. 
The  large  cells  are  the  primitive  ova. 

epithelial  cells.  This  constitutes  a  primary  Graafian  follicle.  Rarely  a  follicle 
contains  more  than  one  ovum.  In  the  case  of  the  egg  nests,  the  ova  may  become 
separated,  or  two  or  more  may  lie  in  one  follicle.  If  two  or  more  ova  are 
present  at  first  in  any  follicle,  usually  only  one  continues  to  develop  and  the 
others  either  degenerate  or  are  used  as  nutritive  materials.  In  very  rare  cases, 
however,  two  ova  may  develop  in  a  single  follicle,  but  whether  they  reach 
maturity  or  not  is  uncertain.  The  formation  of  egg  cords  is  usually  com- 
pleted before  birth,  but  in  some  cases  may  continue  for  one  or  two  years  after 
birth.  During  the  processes  thus  far  described,  the  stroma  also  has  been  in- 
creasing, and  the  egg  cords  and  follicles  come  to  be  separated  by  a  considerable 
amount  of  connective  tissue.  The  germinal  epithelium  becomes  reduced  to  a 
single  layer  of  cuboidal  cells. 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


409 


Each  primary  ovarian  follicle,  containing  a  primitive  ovum  (egg  cell,  sex  cell) , 
is  composed  of  a  single  layer  of  flat  or  cuboidal  cells,  plus  a  layer  of  stroma 
which  gives  rise  to  the  theca  folliculi.  As  the  ovum  continues  to  enlarge,  the 
follicular  cells  become  higher  and  arranged  in  a  radial  manner  (Fig.  369,  a) .  By 
proliferation,  the  follicular  cells  come  to  form  several  layers,  the  innermost 
layer  retaining  the  radial  character  and  forming  the  zona  radiata.  The  inner  or 
basal  ends  of  the  cells  of  the  zona  radiata  become  clear  to  form  the  zona  pellucida. 
In  the  latter,  radial  striations  appear  which  have  been  described  as  minute 


c  d 

FIG.  369. — Four  stages  in  the  development  of  the  ovarian  (Graafian)  follicle 

From  photographs  of  sections  of  a  cat's  ovary      Hertivig. 

The  ovum  is  not  shown  in  a,  b  and  c. 

channels  in  the  cells,  through  which  nutriment  may  pass  to  the  ovum.  After 
the  follicular  epithelium  has  become  several  layers  thick,  a  fluid  substance 
known  as  the  liquor  folliculi,  and  probably  derived  from  the  cells  themselves, 
comes  to  lie  in  little  pools  among  the  cells  (Fig.  369,  b  and  c ) .  While  the  follicle 
as  a  whole  enlarges,  these  pools  gradually  coalesce  and  form  a  single  large  pool 
which  fills  the  interior  of  the  follicle  (Fib.  369,  d).  Thus  the  epithelium  is 
crowded  out  toward  the  periphery  where  it  forms  a  layer  several  cells  in  thick- 
ness, known  as  the  stratum  granulosum.  The  ovum  itself,  with  the  zona  radiata 
and  some  other  surrounding  cells,  is  also  crowded  off  to  the  periphery  of  the 


410  TEXT-BOOK  OF  EMBRYOLOGY. 

follicle.  The  little  elevation  of  the  stratum  granulosum  in  which  the  ovum 
is  embedded  is  known  as  the  cumulus  ovigerus  or  germ  hill  (see  Fig.  18). 

The  primary  ovarian  follicles  at  first  lie  rather  near  the  surface  of  the  ovary, 
but  as  they  enlarge  and  as  the  ovary  enlarges  they  come  to  lie  deeper.  As  the 
follicle  approaches  maturity  it  increases  greatly  in  size  (5=fc  mm.)  and  finally 
extends  through  the  entire  thickness  of  the  cortex,  its  theca  touching  the  tunica 
albuginea. 

In  speaking  of  the  development  of  the  follicles,  it  must  be  remembered  that 
they  develop  slowly  and  do  not  reach  maturity  until  near  the  age  of  puberty,  and 
furthermore  that  one,  or  very  few  at  most,  reach  maturity  at  the  same  time.  In 
other  words,  when  one  follicle  has  reached  maturity  there  are  all  intermediate 
stages  of  development  between  this  and  the  primitive  follicles.  When  a  follicle 
reaches  maturity  it  ruptures  at  the  surface  of  the  ovary  and  the  ovum  is  set  free 
(p.  30).  The  ovum  itself  undergoes  certain  changes  by  which  the  somatic 
number  of  chromosomes  is  reduced  one-half  (p.  21).  It  then  unites  with  the 
mature  spermatozoon,  which  also  contains  one-half  the  somatic  number  of 
chromosomes,  and  forms  the  starting  point,  so  to  speak,  for  a  new  individual. 
At  this  point  the  processes  by  which  an  individual  is  carried  through  its  life 
period  from  its  beginning  as  a  fertilized  ovum  to  the  time  when  it  produces  the 
next  generation  of  mature  sexual  elements  are  ended.  The  developmental 
cycle  of  one  generation  is  complete. 

It  has  been  estimated  that  approximately  36,000  primitive  ova  appear  in 
each  human  ovary.  Since,  as  a  rule,  only  one  ovum  escapes  from  the  ovary  at  a 
menstrual  period  or  between  two  succeeding  periods,  it  is  obvious  that  the  vast 
majority  of  these  never  reach  maturity.  They  probably  degenerate,  and,  as  a 
matter  of  fact,  atretic  follicles  may  be  found  in  an  ovary  at  any  time. 

CORPUS  LUTEUM. — After  the  rupture  of  the  mature  follicle  at  the  surface  of 
the  ovary  and  the  escape  of  the  ovum  and  liquor  folliculi,  blood  from  the  rup- 
tured vessels  fills  the  interior  of  the  follicle  and  forms  a  clot — the  corpus  h&mor- 
rhagicum.  The  cells  of  the  stratum  granulosum  proliferate  and  migrate  into 
the  clot  and  gradually  form  a  mass  which  replaces  the  blood.  It  is  held  by  some 
that  the  cells  are  derived  from  the  theca  folliculi.  Whatever  their  origin,  they 
become  infiltrated  with  a  fatty  substance  known  as  lutein.  Trabeculse  of 
connective  tissue  grow  into  the  mass  of  cells,  carrying  small  blood  vessels  with 
them.  The  (lutein)  cells  disintegrate  and  the  products  of  disintegration  are 
probably  carried  off  by  the  blood,  and  finally  the  entire  corpus  luteum  is  trans- 
formed into  a  mass  of  connective  tissue  (Figs.  19,  20  and  21,  and  p.  31). 

Whether  the  escaped  ovum  is  fertilized  or  not  has  an  influence  upon  the 
development  of  the  corpus  luteum.  In  case  of  fertilization,  the  corpus  luteum 
becomes  quite  large,  increasing  in  size  up  to  the  fourth  month  of  pregnancy,  and 
then  degenerates.  In  case  the  ovum  is  not  fertilized,  the  corpus  luteum  re- 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  411 

mains  smaller.     In  both  cases,  however,  the  histological  changes  are  essentially 
the  same  (p.  33). 

The  Testicle. — The  processes  that  give  rise  to  the  "indifferent"  genital 
glands  have  been  described  (p.  403  et  seq.) .  It  has  also  been  stated  that  there 
appears  during  the  fourth  or  fifth  week  a  structure  that  forms  one  of  the  char- 
acteristic features  of  the  testicle.  This  is  a  layer  of  dense  connective  tissue 
which  develops  beneath  the  surface  epithelium  and  constitutes  the  tunica 
albuginea  (p.  405),  and  which  separates  the  surface  epithelium  from  the  sex 
cords  (Fig.  365) .  The  epithelium  becomes  reduced  to  a  single  layer  of  flat  cells, 
although  the  cells  on  the  tip  of  the  gland  usually  remain  high  until  after  birth. 
Naturally  this  epithelium  is  continuous  around  the  hilus  of  the  testicle  with  the 
epithelium  (mesothelium)  of  the  abdominal  cavity.  Within  the  gland  are  the 
sex  cords — the  progenitors  of  the  convoluted  seminiferous  tubules,  which  become 
quite  distinctly  marked  off  from  the  stroma  by  a  basement  membrane.  In  the 

Interstitial  cell  Sex  cell 


- 
*^-    *    ~*  -~,  *.*--** 


m 


Mesothelium    *Tunica  Supporting  cell 

albuginea  (of  Sertoli) 

FIG.  370. — From  a  section  of  the  testicle  of  a  human  foetus  of  35  mm.,  showing  a  developing 
convoluted  seminiferous  tubule.     Meyer-Rilegg,  Biihler. 

hilus  region  lie  the  rete  cords — the  progenitors  of  the  rete  testis  and  the  straight 
seminiferous  tubules  (Fig.  365) .  The  rete  cords  of  the  testicle  are  homologues  of 
the  rete  cords  of  the  ovary,  and  are  derivatives  of  the  germinal  epithelium  on  the 
cephalic  portion  of  the  "indifferent"  gland  (p.  404). 

The  sex  cords  at  first  are  solid  masses  composed  of  several  layers  of  cells. 
The  latter  are  of  two  kinds,  as  in  the  ovary — (i)  smaller,  darkly  staining  indiffer- 
ent cells,  and  (2)  larger,  clearer  sex  cells  (Fig.  370).  The  sex  cells  lose  their 
clearness  and  come  to  resemble  again  the  undifferentiated  epithelial  cells. 
They  represent  the  spermatogonia,  which  correspond  to  the  primitive  ova. 
The  spermatogonia  proliferate  very  rapidly  and  become  much  more  numerous 
than  the  epithelial  cells.  The  sex  cords  become  more  and  more  coiled  during 
development  and  anastomose  with  one  another  near  the  convex  surface 
of  the  testicle.  Beginning  after  birth  and  continuing  up  to  the  time  of 
puberty,  lumina  appear  in  them  by  displacement  of  the  central  cells,  and 


412  TEXT-BOOK  OF  EMBRYOLOGY. 

they  thus  give  rise  to  the  convoluted  seminiferous  tubules.  The  supporting 
cells  (of  Sertoli)  are  probably  derived  from  the  undifferentiated  epithelial  cells. 

The  details  of  the  further  development  of  the  spermatogonia  to  form  the 
the  spermatozoa  have  been  described  in  the  Chapter  on  Maturation.  At  this 
point,  that  is,  with  the  formation  of  the  spermatozoon,  the  life  cycle  from  a 
mature  male  sexual  element  in  an  individual  to  a  mature  male  sexual  element 
in  an  individual  of  the  succeeding  generation  is  completed. 

The  rete  cords  constitute  an  anastomosing  network  of  solid  cords  of  small, 
darkly  staining  cells,  situated  in  the  hilus  region.  These  cords  later  acquire 
irregular  lumina,  which  are  lined  with  cuboidal  cells,  and  form  the  rete  testis. 
Evaginations  grow  out  from  the  rete  and  fuse  with  the  ends  of  the  convoluted 
tubules,  thus  forming  the  straight  tubules.  On  the  other  hand,  outgrowths 
from  the  rete  unite  with  the  tubules  in  the  cephalic  portion  of  the  mesonephros, 
so  that  a  direct  communication  is  established  between  the  convoluted  semi- 
niferous tubules  and  the  mesonephric  tubules.  There  is  thus  formed  the  proxi- 
mal part  of  the  efferent  duct  system  of  the  testicle  (Fig.  365).  That  portion 
of  the  tunica  albuginea  in  which  the  rete  testis  lies,  becomes  somewhat  thickened 
to  form  the  mediastinum  testis. 

The  stroma  of  the  testicle  is  derived  for  the  most  part  from  the  mesenchyme 
of  the  "indifferent"  gland  or  genital  ridge.  Probably  a  smaller  part  is  derived 
from  the  germinal  epithelium  (see  p.  404).  During  development,  however, 
the  glandular  elements  increase  more  rapidly  than  the  stroma,  so  that  in  the 
adult  they  predominate.  There  is  a  tendency  for  the  convoluted  tubules  to 
become  arranged  in  groups  which  are  separated  by  trabeculae  of  connective 
tissue  radiating  from  the  mediastinum.  The  interstitial  cells  of  the  stroma  are 
direct  derivatives  of  the  connective  tissue  cells  (Fig.  370). 

Determination  of  Sex. 

The  views  regarding  the  determination  of  sex  are  discussed  in  the  chapter 
on  Maturation  (page  27)  in  connection  with  the  question  of  Mendelian 
heredity. 


THE   DEVELOPMENT   OF  THE  UROGEXITAL  SYSTEM. 


413 


The  Ducts  of  the  Genital  Glands  and  the  Atrophy  of  the 
Mesonephroi. 

In  the  Female. — Strictly  speaking,  the  ovaries  are  ductless  glands;  for 
neither  developmentally  nor  anatomically  are  the  ducts  which  convey  their 
specific  secretion  directly  connected  with  them.  Furthermore,  these  ducts  are 
in  part  transformed  into  certain  organs  for  the  reception  and  retention  of  both 
kinds  of  sexual  elements.  In  other  words,  the  ducts  in  part  become  specially 
modified  to  form  the  vagina  and  uterus,  of  which  the  latter  serves  as  an  organ 
of  maintenance  for  the  embryos  of  the  next  generation. 

The  ducts  originate  in  connection  with  the  mesonephroi,  and  are  known  at 
first  as  the  Mullerian  ducts.  They  appear  in  both  sexes  alike  but  persist  only  in 
the  female.  In  the  lower  Vertebrates  they  are  split  off  from  the  mesonephric 
ducts.  In  the  higher  forms,  however,  their  mode  of  origin  is  not  known  with 


Ureter 


Intestine 


Mesonephric  duct 


Liver. 


Genital  cord 

Mullerian  duct 

Left  umbilical  artery 

Bladder 


Right  umbilical  artery 


FIG.  371. — From  a  transverse  section  through  the  pelvic  region  of  a  human  embryo 
of  25  mm.  (82-9  weeks).     Keibel. 

certainty,  but  the  present  evidence  favors  the  view  that  they  arise  independ- 
ently of  the  mesonephric  ducts.  They  appear  in  human  embryos  of  8-14  mm. 
The  mesothelium  on  the  lateral  surface  of  the  cephalic  end  of  each  mesonephros 
becomes  thickened  and  then  invaginates  or  dips  into  the  underlying  mesen- 
chyme.  By  proliferation  of  the  cells  at  its  tip,  the  invaginated  mass  grows 
caudally  as  a  duct  parallel  with  and  close  to  the  mesonephric  duct.  The  two 
ducts  come  to  be  embedded  in  a  ridge  which  at  the  cephalic  end  of  the  meso- 
nephros is  situated  laterally,  but  toward  the  caudal  end  bends  around  and  comes 
to  lie  ventrally.  Beyond  (caudal  to)  the  mesonephros  the  ridge  is  attached  to 
the  lateral  body  wall,  and  near  the  urogenital  sinus  it  meets  and  fuses  with  its 
fellow  of  the  opposite  side  (Fig.  371).  The  two  Mullerian  ducts,  contained 
in  the  ridges,  also  approach  each  other  and  fuse.  The  fusion  begins  in 
embryos  of  25  to  28  mm.  (end  of  second  month),  and  about  the  same  time  they 
open  into  the  dorsal  side  of  the  urogenital  sinus.  The  relations  of  the  Mullerian 


414 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  mesonephric  ducts  are  different  in  different  parts  of  their  courses.  At  the 
cephalic  end  the  Miillerian  lies  dorsal  to  the  mesonephric,  but  farther  back  it 
runs  more  laterally,  then  ventrally,  and  finally  opens  into  the  urogenital  sinus 
on  the  medial  side  of  the  mesonephric  duct. 

THE  OVIDUCT. — The  single  part  of  each  Mullerian  duct  gives  rise  to  the 
oviduct.  The  opening  at  the  cephalic  end  remains  as  the  ostium  abdominale 
tuba,  which  from  the  beginning  communicates  directly  with  the  abdominal 
cavity  (coelom)  and  never  becomes  connected  with  the  ovary  (Fig.  366).  The 
rim  of  the  opening  sends  from  three  to  five  projections  into  the  abdominal 
cavity  to  form  the  primary  fimbrice.  Secondary  branches  grow  out  from  these 
and  form  the  numerous  fimbriae  of  the  adult  oviduct.  The  part  of  each 


Bladder 


Uterus        Rectum 


Symphysis  pubis 


\\  '    '  -  ,••  .;:. 


Cervix  uteri 


Labium  majus  I      Hymen 

Labium  minus 


Vagina 


FIG.  372. — Right  half  of  the  pelvic  region  of  a  female  human  foetus  of  7  months.     Nagel. 

Miillerian  duct  between  the  fimbriated  end  and  the  fused  caudal  end,  grows  in 
length  as  the  embryo  develops,  but  not  proportionately,  so  that  in  the  adult  the 
oviduct  is  relatively  shorter  than  in  the  embryo.  At  first  it  is  lined  with  simple 
cylindrical  epithelium,  but  later  the  cells  become  cuboidal,  and  during  the 
second  half  of  f cetal  life  acquire  distinct  cilia.  The  connective  tissue  and  muscle 
of  the  oviduct  are  derived  from  the  mesenchyme  that  primarily  surrounds  the 
Mullerian  duct. 

In  connection  with  one  of  the  fimbrias  of  the  oviduct  there  is  sometimes  found 
a  small  vesicle  lined  with  ciliated  epithelium,  forming  the  non-stalked  hydatid 
(of  Morgagni),  which  possibly  represents  the  extreme  cephalic  end  of  the 
Miillerian  duct  (Fig.  380).  In  this  case  the  permanent  ostium  of  the  tube 
would  be  of  secondary  origin. 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  415 

THE  UTERUS  AND  VAGINA. — The  fused  caudal  ends  of  the  two  Mullerian 
ducts  form  the  anlage  of  the  uterus  and  vagina,  which  is  a  single  medial  tube 
opening  into  the  urogenital  sinus  (Fig.  363).  During  the  third  month  certain 
histological  changes  bring  about  a  differentiation  between  the  cephalic  end  or 
uterus  and  the  caudal  end  or  vagina.  The  simple  columnar  epithelium  of  the 
vaginal  portion  changes  to  stratified  squamous,  and  during  the  fourth  month 
the  lumen  becomes  closed.  Near  the  external  orifice  a  semicircular  fold  ap- 
pears, which  represents  the  hymen  (Fig.  372).  During  the  sixth  month  the 
lumen  reappears  by  a  breaking  down  of  the  central  cells.  The  epithelium  of 
the  uterus,  primarily  high  columnar,  becomes  lower  and  toward  the  end  of 
foetal  life  acquires  cilia.  Many  irregular  folds  appear  in  the  mucosa  of  the 
vagina,  a  smaller  number  in  the  uterus  (Fig.  372).  Some  of  the  folds  in  the 


Ovary 


Mesovarium 


Broad  ligament 
with  paroophoron 


Oviduct 


Mesosalpinx 
with  epoophoron 


FIG.  373. — Transverse  section  through  the  ovary  and  broad  ligament  of  a  human 
foetus  of  3  months.     Nagel. 

uterus  constitute  the  regular  plica  palmatcz  of  the  cervix.  The  uterine  glands 
represent  evaginations  from  the  epithelial  lining.  They  do  not  begin  to  develop 
until  after  birth  (one  to  five  years),  and  their  development  is  usually  not  com- 
pleted until  the  age  of  puberty. 

The  muscle  and  connective  tissue  of  the  walls  of  the  uterus  and  vagina  are 
derived  from  the  mesenchyme  which  surrounds  the  Mullerian  ducts.  The 
muscle  develops  relatively  late  (after  the  fourth  month  of  foetal  life). 

ATROPHY  OF  THE  MESONEPHROI. — By  far  the  greater  part  of  each  meso- 
nephros  degenerates  and  disappears,  and  the  parts  that  do  persist  are  rudimentary 
and  possess  no  functional  significance.  The  cephalic  portion  leaves  ten  to 
twenty  coiled  tubules  which  terminate  blindly  at  one  end  and  at  the  other  end 
open  into  a  common  duct  that  represents  the  cephalic  end  of  the  mesonephric 
duct.  These  tubules  constitute  the  epoophoron  (parovarium,  organ  of  Rosen- 


416  TEXT-BOOK  OF  EMBRYOLOGY. 

miiller)  which  comes  to  lie  in  the  mesosalpinx  between  the  oviduct  and  the 
mesovarium,  and  later  in  the  mesentery  between  the  oviduct  and  the  ovary 
(Fig.  373).  At  the  height  of  their  development  the  tubules  are  lined  with 
columnar,  ciliated  epithelium.  The  rete  cords  of  the  ovary  (rete  ovarii,  p.  407) 
during  their  development  unite  with  the  tubules  in  the  cephalic  portion  of  the 
mesonephros,  but  later  disappear.  The  epoophoron  is  homologous  with  the 
tubules  of  the  head  of  the  epididymis  in  the  male. 

The  caudal  portion  of  the  mesonephros  leaves  a  few  tubular  remnants 
which  come  to  lie  in  the  broad  ligament  near  the  hilus  of  the  ovary.  These  con- 
stitute the  paroophoron  which  is  homologous  with  the  paradidymis  in  the  male 
(Fig.  373).  They  may  disappear  before  birth  or  may  persist  through  life. 

The  mesonephric  duct  also  leaves  certain  remnants  which  are  situated  (i)  in 
the  broad  ligament,  (2)  in  the  lateral  wall  of  the  uterus,  (3)  in  the  lateral  wall  of  the 
vagina,  and  (4)  in  the  tissue  lateral  to  the  external  genital  opening.  These  rem- 
nants are  known  as  the  canals  of  Gartner,  and  they  naturally  lie  in  the  course  of 
the  duct  in  the  embryo.  All  the  rudimentary  structures  derived  from  the 
mesonephroi  and  their  ducts  are  extremely  variable. 

In  the  Male. — In  the  male  all  the  efferent  ducts  of  the  genital  glands,  except 
the  rete  testis,  are  derived  from  the  mesonephroi  and  their  ducts.  As  described 
earlier  in  this  chapter  (p.  411),  the  rete  testis  acquires  a  connection  with  some  of 
the  tubules  in  the  cephalic  end  of  the  mesonephros  and  with  the  sex  cords  or 
anlagen  of  the  convoluted  and  straight  seminiferous  tubules  (see  Fig.  365). 
This  establishes  a  communication  between  the  seminiferous  tubules  and  the 
tubules  of  the  mesonephros.  Those  mesonephric  tubules  with  which  the  rete 
testis  unites  persist  as  the  efferent  ductules  (or  vasa  eff erentia) .  The  latter  form 
a  set  of  coiled  ducts  which  are  situated  in  the  head  of  the  epididymis  and  which 
open  into  the  cephalic  part  of  the  mesonephric  duct  (Fig.  347).  They  are 
homologous  with  the  epoophoron  in  the  female. 

The  next  succeeding  portion  of  the  mesonephric  duct  becomes  the  duct  of  the 
epididymis  which  in  its  tortuous  course  constitutes  the  bulk  of  the  body  and  tail 
of  the  epididymis  and  passes  over  into  the  caudal  portion  of  the  mesonephric 
duct.  The  latter  portion  becomes  the  deferent  duct  (vas  def erens) .  The  caudal 
end  of  the  deferent  duct  forms  the  ejaculatory  duct  which  opens  into  the  urogeni- 
tal  sinus.  The  seminal  vesicles  appear  during  the  third  month  as  lateral 
evaginations  from  the  ejaculatory  ducts. 

The  portions  of  the  mesonephros  not  involved  in  the  formation  of  the  duct 
system  of  the  testicle  atrophy  and  for  the  most  part  disappear.  They  leave 
certain  tubules,  however,  which  persist  as  rudimentary  structures  connected 
with  the  testicle.  In  the  cephalic  end,  some  of  the  tubules  persist  in  part  and 
come  to  lie  among  the  efferent  ductules,  being  either  attached  to  the  latter  or  un- 
connected, and  forming  the  appendage  of  the  epididymis.  The  caudal  part  of 


THE  DEVELOPMENT  OF  THE  UROGEXITAL  SYSTEM. 


417 


the  mesonephros  leaves  a  few  tubules  which  come  to  lie  near  the  head  of  the  epi- 
didymis  and  form  the  paradidymis  (or  organ  of  Giraldes) ,  the  tubules  of  which 
are  lined  with  columnar,  ciliated  epithelium.  Near  the  transition  from  the 
duct  of  the  epididymis  to  the  deferent  duct  there  is  almost  invariably  a  tubule 
(sometimes  branched)  which  also  represents  a  remnant  of  the  mesonephros  and 
is  known  as  the  aberrant  ductule.  It  usually  opens  into  the  duct  of  the  epididy- 
mis, but  may  lie  free  in  the  tissue  around  it  (Fig.  347). 

ATROPHY  OF  THE  MULLERIAN  DUCTS. — These  ducts  persist  in  the  female 
and  become  the  oviducts,  uterus  and  vagina;  in  the  male  they  degenerate  and 
disappear  almost  entirely.  The  degeneration  begins  about  the  time  they  open 


Diaphragmatic 
ligament  of 
mesonephros 


Genital  gland 


Mesonephros 


Mesonephric  duct 


Urachus 


Mesonephric  duct 


Inguinal  ligament 


Umbilical  artery 
FIG.  374. — Crogenital  organs  in  a  human  embryo  of  17  mm.  (6  weeks).     Kollmann's  Atlas. 

into  the  urogenital  sinus  (embryos  of  25  to  28  mm.) ;  by  the  time  the  embryo 
reaches  a  length  of  60  mm.  only  the  extreme  cephalic  end  and  the  caudal 
third  remain,  and  at  90  mm.  the  entire  duct  is  gone  except  the  extreme  ends. 
The  cephalic  end  persists  as  the  appendix  testis  (or  hydatid  of  Morgagni) 
(Figs.  347,  379).  The  caudal  end  persists  as  the  utriculus  prostaticus  (uterus 
masculinus). 

Changes  in  the  Positions  of  the  Genital  Glands  and  the  Development 

of  their  Ligaments. 

During  the  early  stages  of  development  the  genital  glands — testicles  or 
ovaries — are  situated  far  forward  in  the  abdominal  cavity.  During  the  eighth 
week  they  lie  opposite  the  lumbar  vertebrae.  During  the  succeeding  months, 
up  to  the  time  of  birth,  they  gradually  move  caudally  to  the  positions  they 


418 


TEXT-BOOK  OF  EMBRYOLOGY. 


occupy  in  the  adult.  This  migration  is  brought  about,  to  some  extent  at 
least,  by  the  influence  of  certain  bands  of  tissue  which  are  primarily  like 
mesenteries.  As  the  mesonephros  develops  and  projects  into  the  body  cavity. 


Ureter 


Deferent  duct 

Inguinal  ligament 
(Gubernaculum  testis) 

Processus  vaginalis 
peritonasi 


.-•-Umbilical  cord 


FIG.  375. — From  a  dissection  of  the  pelvic  region  of  a  male  human  foetus  of  21  cm. 

Kollmanri's  Atlas. 

it  comes  to  be  attached  along  the  dorsal  body  wall,  lateral  to  the  dorsal  mesen- 
tery, by  a  sheet  of  tissue  which  is  called  the  mesonephric  mesentery.  Cranial  to 
the  mesonephros,  this  mesentery  is  continued  as  the  diaphragmatic  ligament 


1>- Spermatic  cord 

A 

••'  \ 

*n        Inguinal  ring 


Tunica  vaginalis 


Tunica  vaginalis 

communis 


Inguinal  cone 


Scrotum 


Raphe* 


FIG.  376. — From  a  dissection  of  the  scrotal  region  of  a  human  foetus  of  25  cm. 
Kollmann's  Atlas. 

of  the  mesonephros,  which  as  the  name  indicates,  is  attached  to  the  diaphragm; 
caudally  it  is  continued  to  the  inguinal  region  as  the  inguinal  ligament  of  the 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


419 


mesonephros  (Fig.  374).  The  genital  gland  lies  on  the  medial  side  of  the 
mesonephros  and  is  attached  to  the  latter  by  a  sort  of  mesentery  which  becomes 
the  mesovarium  in  the  female  or  the  mesorchium  in  the  male.  The  cephalic 
portions  of  the  ducts  (Miillerian  and  mesonephric)  lie  close  together  in  a  ridge 
on  the  lateral  surface  of  the  mesonephros;  as  they  pass  caudally  they  extend 
around  to  the  ventral  surface  of  the  mesonephros  and  approach  the  medial  line, 
and  finally,  in  the  pelvic  region,  the  two  ridges  meet  and  fuse,  forming  the  so- 
called  genital  cord  (Fig.  371).  The  genital  cord  thus  contains  the  mesonephric 
and  Mullerian  ducts,  the  latter  fusing  to  form  a  single  tube  (the  anlage  of  the 
uterus  and  vagina,  p.  415).  It  also  contains  the  umbilical  arteries. 


Kidney 


Suprarenal  gland 


Intestine 


Round  ligament 
("Inguinal  ligament) 


Umbilical  artery 


Umbilical  vein 


FlG«  377- — From  a  dissection  of  the  pelvic  region  of  a  female  human  foetus  of  7.5  cm. 

Kollmann's  Atlas. 

Such  a  condition  is  found  in  embryos  of  about  eight  weeks.  From  this 
time  on,  the  processes  of  development  follow  divergent  lines  in  the  two  sexes, 
the  differences  becoming  more  marked  from  month  to  month.  Certain  struc- 
tures persist  and  other  disappear,  according  to  the  sex.  The  mesenteries  and 
ligaments  undergo  metamorphoses  and  the  genital  glands  migrate  caudally. 

Descent  of  the  Testicles.— As  the  mesonephros  atrophies,  its  mesentery 
and  the  mesentery  of  the  testicle  are  combined  to  form  a  single  band  of  tissue 
which,  of  course,  is  continuous  with  the  inguinal  ligament.  The  latter  now 
becomes  the  so-called  gubernaculum  testis  (Hunteri),  a  strong  band  or  cord 
composed  of  connective  tissue  and  smooth  muscle.  Its  cephalic  end  is  attached 
to  the  epididymis;  its  caudal  end  pierces  the  body  wall  in  the  inguinal  region  and 


420 


TEXT-BOOK  OF  EMBRYOLOGY. 


is  attached  to  the  corium  of  the  skin  (Fig.  375).  It  plays  an  important  part  in 
the  descent  of  the  testicle.  The  descent  is  brought  about  through  the  principle 
of  unequal  growth.  As  the  body  grows  in  length,  the  gubernaculum  grows 
much  less  rapidly  and,  since  the  caudal  end  of  the  latter  is  fixed,  the  natural 
result  is  the  drawing  downward  of  the  testicle.  This  takes  place  gradually, 
and  at  the  end  of  the  third  month  the  testicle  lies  in  the  false  pelvis ;  at  the  end 
of  the  sixth  month  close  to  the  body  wall  at  the  inguinal  ring. 

During  the  third  month  a  second  factor  in  the  descent  of  the  testicle  appears. 
This  is  an  evagination  of  the  peritoneum  at  the  point  where  the  gubernaculum 
pierces  the  body  wall.  The  evagination  at  first  is  a  shallow  depression,  known 


Kidney 
Mullerian  duct 

Genital  gland 
Mesonephros 


Ureter 

Inguinal  ligament 

Mesonephric  duct 

Mullerian  duct 


Apex  of  bladder 
Bladder 
Opening  of  ureter 


Opening  of  mesonephric  duct 

Opening  of  Mullerian  ducts 

Rectum 

Urogenital  sinus 

Cloaca 

Genital  tubercle 

Genital  ridge 

Opening  of  cloaca 


FIG.  378. — Diagrammatic  representation  of  the  urogenital  organs  in  the  "  indifferent "  stage.  Hertivig* 


as  the  processus  vaginalis  peritonei,  but  continues  to  burrow  through  the  body 
wall  and  causes  an  elevation  in  the  skin  which  is  destined  to  become  one  side  of 
the  scrotum  (see  p.  426) .  The  opening  of  the  peritoneal  sac  into  the  body  cavity 
is  the  inguinal  ring.  In  its  descent  the  testicle  passes  through  the  inguinal  ring 
and  comes  to  lie  in  the  elevation  in  the  skin  or  scrotum  (ninth  month) .  Whether 
its  passage  into  the  scrotum  is  the  result  of  a  traction  by  the  gubernaculum  is 
not  certain.  The  inguinal  ring  then  closes  by  apposition  of  its  walls  and  the 
testicle  lies  in  a  closed  sac  which  has  been  pinched  off,  so  to  speak,  from  the  body 
cavity  (Fig.  376). 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


421 


Kidney 

Appendage  of  testicle 
(hydatid  of  Morgagm) 

Epididymis 

Testicle 

Paradidymis 

Deferent  duct 

Mullerian  duct 

Gubernaculum  testis 

Ureter 

Seminal  vesicle 
Deferent  duct 


Epididymis 
Testicle 

Gubernaculum  testis 


Kidney 


Hydatid 

Oviduct 
(fimbrise) 

Epoophoron 
Ovary 

Paroophoron 

Mesonephric  duct 

Oviduct 

Epoophoron 

Ovary 

Ovarian  ligament 

Uterus 
Round  ligament 


Vagina 


Apex  of  bladder 


Bladder 

Opening  of  ureter 

Urethra 

Opening  of  ejacul.  duct 

Prostate 


Urethra    Sinus  prostaticus 

FIG.  379. 


Apex  of  bladder 


Urethra 
Vestibulum  vaginae 


FlG.  380. 


FIG.  379. — Diagram  of  the  development  of  the  male  genital  organs  from  the 

;<  indifferent "  anlagen.     Hertuuig. 
FIG.  380. — Diagram  of  the  development  of  the  female  genital  organs  from  the 

"  indifferent "  anlagen.     Hertwig. 

These  diagrams  should  be  compared  with  Fig.  378.  The  dotted  lines  represent  the  organs  in  the 
relative  positions  they  occupy  in  the  adult  (with  the  exception  of  the  Miillerian  duct  in  the 
male  and  the  mesonephric  duct  in  the  female,  which  ducts  disappear  for  the  most  part). 


422  TEXT-BOOK  OF  EMBRYOLOGY. 

Since  the  testicle  is  invested  by  peritoneum  from  the  beginning  of  its  develop- 
ment, it  must  be  understood  that  in  its  passage  into  the  scrotum  it  passes  along 
under  the  peritoneum.  Consequently  when  it  reaches  the  scrotum  it  is  sur- 
rounded by  a  double  layer  of  peritoneum,  the  tunica  vaginalis  propria. 

The  descent  of  the  testicle  also  produces  marked  changes  in  the  course  of 
the  deferent  duct.  Primarily  the  (mesonephric)  duct  extends  cranially  from 
the  urogenital  sinus  in  a  longitudinal  direction.  But  as  the  testicle  migrates, 
the  cephalic  end  of  the  duct  is  drawn  caudally  so  that  in  the  adult  the  deferent 
duct  extends  cranially  from  the  scrotum  to  the  ventral  side  of  the  urinary 
bladder  and  then  bends  caudally  again  to  open  into  the  urethra. 

Descent  of  the  Ovaries. — The  ovaries  undergo  a  change  of  position  cor- 
responding to  the  descent  of  the  testicles,  although  the  change  is  not  so  extensive. 
Primarily  the  Miillerian  and  mesonephric  ducts  lie  in  a  ridge  on  the  surface  of 
the  mesonephros  (p.  413).  As  the  mesonephros  and  its  duct  atrophy,  the  Miil- 
lerian duct  (oviduct)  comes  to  lie  in  a  fold,  the  mesosalpinx,  which  is  attached 
to  the  mesovarium  (Fig.  373) .  At  the  same  time  the  mesovarium  becomes  directly 
continuous  with  and  really  a  part  of  the  inguinal  ligament.  The  latter  cor- 
responds, of  course,  to  the  gubernaculum  testis,  and  plays  a  role  in  the  descent 
of  the  ovaries.  It  may  be  conveniently  divided  into  three  parts,  (i)  a  cephalic 
part  which  is  attached  to  the  hilus  of  the  ovary,  (2)  a  middle  part  which  ex- 
tends from  the  ovary  to  the  uterus,  forming  the  ovarian  ligament,  and  (3)  a  cau- 
dal part  which  extends  from  the  uterus  to  the  inguinal  region,  forming  the 
round  ligament  of  the  uterus  (Fig.  377).  The  round  ligament  pierces  the  body 
wall  and  is  attached  to  the  corium  of  the  skin.  At  the  point  where  it  passes 
through  the  body  wall  there  is  a  slight  evagination  of  the  peritoneum,  the 
diverticulum  of  Nuck,  which  corresponds  to  the  processus  vaginalis  peritonei 
in  the  male. 

The  ovaries  gradually  migrate  caudally  from  their  original  position  into  the 
false  pelvis  (third  month)  and  thence  into  the  true  pelvis  (at  birth).  Obviously 
no  traction  can  be  exerted  upon  them  by  the  round  ligament  (or  caudal  part  of 
the  inguinal  ligament),  since  the  latter  extends  from  the  uterus  to  the  inguinal 
region.  Their  descent  into  the  pelvic  seems  to  be  due  to  the  unequal  growth 
of  the  ovarian  ligaments,  or  in  other  words,  to  the  fact  that  the  ovarian  liga- 
ments grow  proportionally  less  than  the  surrounding  parts.  During  their 
descent  the  ovaries  become  embedded  in  the  broad  ligaments  of  the  uterus, 
which  represent  further  development  of  the  peritoneal  folds  of  the  genital  cord. 
In  this  way  the  mesovarium  becomes  merged  with  the  broad  ligament. 

On  pages 420  and  421  are  three  diagrammatic  representations  of  the  changes 
that  take  place  in  the  genital  systems  of  the  two  sexes.  Fig.  378  represents 
the  " indifferent "  stage  in  which  all  the  embryonic  structures  are  present; 
Fig.  379  represents  the  changes  that  occur  in  the  male;  Fig.  380  represents  the 


THE  DEVELOPMENT  OF  THE  UROGEXITAL  SYSTEM. 


423 


changes  that  occur  in  the  female.  A  careful  study  of  the  diagrams  will  assist 
the  student  materially  in  understanding  the  processes  of  development  which 
have  been  described  in  the  preceding  paragraphs. 

Below  is  a  table  that  is  meant  to  set  forth  briefly  the  various  structures 
which  belong  to  the  internal  genital  organs  in  the  two  sexes,  and  which  are 
derived  from  the  structures  in  the  "indifferent"  stage.  The  words  in  italics 
are  the  names  of  structures  that  persist  in  a  rudimentary  form. 


Indifferent 


Male 


Female 


Germinal  epithelium  (meso- 

Convoluted  seminiferous  tubules  1 
with  spermatozoa      / 

Ovarian   (Graafian)  follicles 
with  ova. 

Medullary  cords 

Straight  seminiferous  tubules  .    .   1 
Rete  testis  j 

Rete  cords. 

Part  of  stroma  of  testicle     .... 

Part  of  stroma  of  ovary. 

f  cephalic  part  • 
Mesonephros  \ 
[  caudal  part    < 

r 

i 

i 

Efferent  ductules  (vasa  efferentia)  \ 
A  ppendage  of  epididymis     .    .    .   J 
Paradidymis  (organ  of  Giraldes)  \ 
Aberrant  ductules(vasa  aberrantia)  J 

EpoopJioron,  transverse  duc- 
tules. 

Paroophoron. 

Duct  of  epididymis  (vas  epididy- 
midis)      

Vesicular     appendage     (of 
Morgagni}  (?) 

Mesonephric  duct     .    .    .    .   < 

Deferent  duct  (vas  deferens)  .    . 
Ejaculatorv  duct 

Epoophoron,       longitudinal 
duct. 

Seminal  vesicle 

Gartner's  canals. 

t 

Morgagnfs  appendage  of  testicle  1 
(hydatid  of  Morgagni)      .    .    .   j 

Fimbriae  of  oviduct 
Oviduct. 

. 

Prostatic  utricle  (uterus  masculinus) 

Uterus. 
Vagina. 

Inguinal  ligament  of   meso-  " 
nephros 

\ 

Gubernaculum  testis  (Hunteri)  .    . 

k  Ovarian  ligament. 
Round  ligament  of  uterus. 

Urethra  (prost?ticpart  •    •    •    •   ) 
\  membranous  part    .    .   J 

Prostate  

f  Urethra. 
\  Vestibule  of  vagina. 
Prostate. 

Bulbo-urethral  gland  (Cowpers) 

Larger  vestib  alar  gland  (Bar* 
tholin's. 

THE  EXTERNAL  GENITAL  ORGANS. 

In  addition  to  the  internal  organs  of  generation,  to  which  the  description  has 
thus  far  been  confined,  certain  other  structures  appear  on  the  outside  of  the 
body  to  form  the  external  genitalia.  In  the  case  of  these  also  there  is  an  "indif- 
ferent" stage  from  which  the  courses  of  development  diverge  in  the  two  sexes. 

During  the  sixth  week  a  depression  appearing  on  the  ventral  surface  of  the 
caudal  end  of  the  body  indicates  the  position  of  the  cloacal  membrane  (p.  400). 
This  becomes  surrounded  by  a  slight  elevation,  produced  by  the  thickening 
of  the  mesoderm  which  is  known  as  the  genital  ridge  (Fig.  381).  The  cephalic 


424  TEXT-BOOK  OF  EMBRYOLOGY. 

side  of  the  ridge  becomes  raised  still  farther  above  the  surface,  forming  a  dis- 
tinct protrusion,  the  genital  tubercle.  The  tubercle  continues  to  increase  in 
size,  and  the  distal  end  forms  a  knob-like  enlargement.  Along  the  ventral  (or 
rather  caudal)  side  a  groove  appears,  which  extends  distally  as  far  as  the  base 
of  the  enlarged  end.  The  ridges  along  the  sides  of  the  groove  increase  in 
size  and  form  the  genital  folds.  In  the  meantime  a  second  pair  of  elevations 
appears  lateral  to  the  genital  folds  to  form  the  genital  swellings  (Fig.  382). 

After  the  cloacal  membrane  ruptures,  a  single  opening  is  produced  which 
leads  from  the  exterior  into  the  cloaca.  This  opening  is  then  separated  by  the 
further  growth  of  the  urorectal  fold  (p.  400)  into  the  opening  of  the  urogenital 
tract  and  the  anal  opening.  The  caudal  part  of  the  fold  then  enlarges  to  form 
the  perineal  body,  which  serves  to  push  the  anus  farther  away  from  the  genital 
ridges.  The  latter,  together  with  the  genital  tubercle  and  swellings,  all  of  which 
lie  in  the  immediate  vicinity  of  the  urogenital  opening,  constitute  the  anlagen 
of  the  external  genital  organs  (Fig.  383).  These  at  this  time  are  in  the 
"indifferent"  stage,  from  which  development  proceeds  in  one  of  two  directions, 
accordingly  as  the  embryo  is  a  male  or  a  female.  Up  to  the  fourth  month 
there  is  little  difference  between  the  structures  in  the  two  sexes.  After  this  the 
differences  become  more  and  more  obvious. 

In  the  female  the  changes  in  the  originally  "indifferent"  structures  are 
comparatively  slight.  The  genital  tubercle  grows  slowly  and  becomes  the 
clitoris.  The  enlarged  extremity  becomes  more  clearly  marked  off  from  the 
other  part  to  form  the  glans  clitoridis.  The  skin  covering  the  glans  is  converted 
by  a  process  of  folding  into  a  sort  of  prepuce.  The  genital  folds,  which 
bound  the  opening  of  the  urogenital  tract,  become  elongated  and  form  the 
labia  minora.  The  opening  of  the  urogenital  tract  is  the  vestibulum  vagina. 
The  genital  swellings  enlarge  still  more  than  the  genital  folds,  by  a  deposition 
of  a  considerable  mass  of  fat  in  the  mesenchyme,  and  become  the  labia  majora. 
The  latter  are  the  structures  (mentioned  on  p.  420)  which  mark  the  points 
at  which  the  inguinal  ligaments  of  the  mesonephroi  pierce  the  body  wall,  and 
are  homologous  with  the  scrotum  in  the  male  (Figs.  384  and  385). 

In  the  male  the  "indifferent"  anlagen  undergo  more  extensive  changes 
than  in  the  female.  The  genital  tubercle  continues  to  grow  more  rapidly  and 
forms  the  penis,  which  is  homologous  with  the  clitoris.  The  enlarged  extremity 
becomes  the  glans  penis,  and  an  extensive  folding  of  the  skin  over  the  glans 
forms  the  prepuce.  The  groove  on  the  caudal  or  lower  side  of  the  tubercle 
elongates  as  the  latter  elongates  and  becomes  deeper.  Finally  the  ridge  (or 
genital  fold)  on  each  side  of  the  groove  meets  and  fuses  with  its  fellow  of  the 
opposite  side,  thus  enclosing  within  the  penis  a  canal — the  penile  portion  of 
the  urethra.  The  groove  is  primarily  continuous  with  the  opening  of  the  uro- 
genital tract,  and  as  the  fusion  takes  place  the  penile  portion  forms  a  direct 


Gen.  r. 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  425 

Umb.  c. 

"••:<   ..^ 

^ 

-*.'.—  Umb.  c. 

Gen.  tub. 


do.  and 
gen.  f. 


GI.  p. 


FIG.  385.  FIG.  386. 

FIGS.  381-386. — Stages  in  the  development  of  the  external  genital  organs.     Kollmann's  Atlas. 
FIG.  381,  "  indifferent  "  stage — embryo  of  17  mm.;  Fig.  382,  "  indifferent "  stage — embryo  of  23  mm-; 

Fig.  383,  "  indifferent "  stage — embryo  of  29  mm.  (beginning  of  3d  month);  Fig.  384,  female 

embryo  of  70  mm.  (n  weeks);  Fig.  385,  female  embryo  of  150  mm.  (16  weeks);  Fig.  386, 

male  embryo  of  145  mm.  (16  weeks). 
An.y  Anus;  Cl.,  clitoris;  Clo.and  gen.  /.,  cloaca  and  genital  folds;  CL  m.,  cloacal  membrane;  Ext., 

lower  extremity;    Gen.  /.,  genital  folds;  Gen.  r.,  genital  ridge;    Gen.  yw.,  genital  swelling; 

Gen.  tub.,  genital  tubercle;  Gl.  p.,  glans  penis;  Lab.  ma.,  labium  majus;  Lab.  mi.,  labiura 

minus;    Ra.,  raphe  of  scrotum;    Scr.,  scrotum;  Ta.,  tail;  Ug.  s.,  urogenital  sinus;  Umb.  c^ 

umbilical  cord. 


426  TEXT-BOOK  OF  EMBRYOLOGY. 

continuation  of  the  internal  (membranous  and  prostatic)  portion  of  the  urethra. 
The  genital  swellings  also  fuse  and  form  the  scrotum,  the  line  of  fusion  in  the 
medial  line  becoming  the  raphe  (Fig.  386).  Primarily  the  inguinal  ligaments 
of  the  mesonephroi  are  attached  to  the  corium  of  the  skin  in  the  genital  swellings, 
and  as  the  testicles  descend  they  pass  through  the  inguinal  ring  into  the  scro- 
tum. In  a  sense  the  scrotum  represents  an  evagination  of  the  body  wall 

THE  DEVELOPMENT  OF  THE  SUPRARENAL  GLANDS. 

Although  the  suprarenal  glands  do  not  logically  come  under  the  head  of  the 
urogenital  system,  being  neither  functionally  nor  developmentally  a  part  of  the 
latter,  it  is  most  convenient  to  consider  them  in  this  chapter. 

In  Mammals  including  man  these  glands  are  composed  of  two  parts  which 
can  be  differentiated  histologically  and  topographically — the  cortex  and 
medulla.  The  cortex  is  composed  of  trabeculae  and  spheroidal  masses  of  cells 


Phaeochrome  cells 
i 


Nerve  fibers 


\ 

Phaeochrome    Connective  Sympathetic 

cells  tissue  ganglion  cells 

FIG.  387. — Section  of  a  sympathetic  ganglion  in  the  cceliac  region  of  a  frog  (Rana  esculenta), 
showing  differentiating  phaeochrome  cells.     Giacomini. 

which  do  not  have  a  strong  affinity  for  the  ordinary  cytoplasmic  stains  and 
which  contain  granules  of  a  fat-like  substance  known  as  lipoid  granules.  The 
medulla  is  composed  of  irregularly  arranged  sympathetic  ganglion  cells  and 
other  granular  cells  which,  after  treatment  with  chrome  salts,  acquire  a  peculiar 
brownish  color.  The  brown  cells  are  known  as  chromaffin  (or  phaeochrome) 
cells  and  their  granules  as  chromaffin  (or  phaeochrome)  granules.  As  cortex 
and  medulla  are  distinct  anatomically,  they  are  also  distinct  developmentally, 
being  derived  from  two  distinct  and  different  parent  tissues  which  unite 
secondarily.  Furthermore,  it  is  an  interesting  fact  that  in  the  lower  Vertebrates 
(Fishes)  the  two  parts  remain  permanently  separate;  that  in  the  ascending 
scale  of  animal  life  (Amphibia,  Reptiles,  Birds)  they  become  more  closely 
associated;  and  that  finally  (in  Mammals)  they  unite  to  form  a  single  glandular 
structure.  In  Mammals  the  phylogenetic  history  is  repeated  with  remarkable 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


427 


precision  during  the  development  of  an  individual :  The  two  parts  arise  sepa- 
rately, come  closer  together,  and  finally  unite. 

The  Cortical  Substance. — The  cortex  is  of  mesothelial  (mesodermal) 
origin.  In  embryos  of  five  to  six  mm.  the  mesothelium  at  the  level  of  the 
cephalic  third  of  the  mesonephros  proliferates  and  sends  buds  or  sprouts  into 
the  mesenchyme  at  each  side  of  the  root  of  the  dorsal  mesentery.  These 
sprouts  soon  lose  their  connection  with  the  parent  mesothelium  and  unite  with 
one  another  to  form  a  rather  compact  mass  of  epithelial-like  cells  ventro-lateral 
to  the  aorta  (Fig.  314).  Frequently  the  two  masses  fuse  across  the  medial  line 
ventral  to  the  aorta.  They  constitute  the  anlagen  of  the  cortical  substance  of 


Connective  tissue  •— MS 


Cortex 


Medulla 
(Phaeochrome  cells) 


FIG.  388. — From  a  transverse  section  of  a  40  mm.  pig  embryo,  showing  the  growth  of  the  medullary 
substance  into  the  cortical  substance  of  the  suprarenal  gland.  The  vessel  in  the  center  of 
the  figure  is  the  aorta.  Wiesel. 

the  two  suprarenal  glands.  From  the  fact  that  in  the  lower  forms  they  remain 
separate  from  the  medullary  substance  and  lie  between  the  urinary  organs, 
they  are  known  as  the  interrenal  organs. 

The  Medullary  Substance. — A  little  later  than  the  appearance  of  the 
cortical  anlage,  the  cells  of  some  of  the  developing  sympathetic  ganglia  become 
differentiated  into  two  types — (i)  the  so-called  sympathoblasts  which  develop  into 
sympathetic  ganglion  cells,  and  (2)  ph&ochromoblasts  which  are  destined  to  give 
rise  to  the  phceochome  or  chromafiin  cells  (Fig.  387).  Hence  the  chromafrin 
cells  are  derivatives  of  the  ectoderm,  since  the  ganglia  are  of  ectodermal  origin. 
They  soon  become  more  or  less  separated  from  the  ganglia,  migrate  to  the 


428 


TEXT-BOOK  OF  EMBRYOLOGY. 


region  of  the  cortical  anlagen  and  then  penetrate  the  latter  in  cord-like  masses 
(Fig.  388) .  Finally  these  masses  unite  in  the  interior  of  the  cortical  substance 
to  form  a  single  compact  mass  (Fig.  389).  Along  with  the  phaeochrome  masses, 
sympathoblasts  also  are  carried  in  and  give  rise  to  the  sympathetic  ganglion  cells 
within  the  gland.  The  two  types  of  cells  together  constitute  the  medullary 
substance.  In  the  lower  forms  the  phseochrome  masses  remain  separate  from 
the  cortical  substance  and  are  known  as  the  suprarenal  organs.  In  Mammals 
the  two  sets  of  organs  (interrenal  and  suprarenal)  unite  to  form  the  suprarenal 
gland. 


|£fe 

ill 


'>s-''-'#  V:'.??V^v   '*V 


Med.     Cor.     Cor.1 

FIG.  389. — Section  of  the  suprarenal  gland  of  a  119  mm.  pig  embryo.     Cor.,  Cortex;  Cor.*,  some 
cortical  substance  in  the  center  of  the  gland;  Med.,  medulla.     Wiesel. 

At  the  time  when  the  mesonephros  is  fully  developed,  the  cortical  substance 
forms  a  small  oval  body  near  its  cephalic  end.  During  the  union  of  the  cortex 
and  medulla  and  the  atrophy  of  the  mesonephros,  the  suprarenal  gland  becomes 
more  closely  associated  with  the  cephalic  end  of  the  kidney,  and  by  the  middle  of 
the  third  month  has  practically  reached  its  adult  position.  During  the  third 
month  and  the  first  half  of  the  fourth  month  the  glands  increase  in  size  and 
become  relatively  large  structures,  larger  in  fact  than  the  kidneys.  From  the 
fourth  month  on,  they  grow  proportionately  less  than  the  neighboring  organs, 
and  by  the  sixth  month  are  about  half  as  large  as  the  kidneys.  At  birth  the 
ratio  of  their  weight  to  that  of  the  kidneys  is  about  1:3;  in  the  adult  about  i :  28. 

While  perhaps  in  a  normal  course  of  development  all  the  anlagen  are  united 
in  the  adult  suprarenal  gland,  it  is  not  unusual  to  find  accessory  structures  in 
various  places.  Some  of  these  consist  of  cortical  tissue  only  and  are  usually 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM. 


429 


found  in  or  near  the  capsule  of  the  gland.  Others  may  consist  of  both  cortical 
and  medullary  substances,  and  are  found  in  the  vicinity  of  or  embedded  in  the 
kidneys,  in  the  retroperitoneal  tissue  near  the  kidneys,  in  the  walls  of  neighbor- 
ing blood  vessels,  or  associated  with  the  internal  genital 
organs — in  the  rete  testis  or  epididymis,  or  in  the  broad 
ligament.  These  accessory  structures  may  arise  inde- 
pendently of  the  main  gland,  or  they  may  be  portions  of 
the  main  gland  which  were  separated  during  the  union 
of  the  different  anlagen  of  the  latter  and  were  carried 
away  in  the  descent  of  the  genital  glands. 

In  addition  to  the  chromamn  tissue  which  enters  into 
the  formation  of  the  main  gland  or  of  accessory  glands, 
there  are  other  small  masses  of  this  tissue  which  remain 
permanently  associated  with  some  of  the  prevertebral 
and  peripheral  sympathetic  ganglia. 

Recent  researches  have  shown  that  the  Carotid  Skein 
(glomus  caroticum,  intercarotid  ganglion,  carotid  gland) , 
which  formerly  was  believed  to  be  a  derivative  of  the 
epithelial  lining  of  one  of  the  branchial  grooves,  is  of 
sympathetic  origin  and  that  the  cells  acquire  the  charac- 
teristic chromamn  reaction.  These  facts  indicate  that 
it  is  closely  allied  with  the  medullary  substance  of  the  suprarenal  gland. 


FIG.  390. — Diagram  of 
the  developing  phoeo- 
chrome  masses  in  a 
human  foetus  of  50 
mm.  Ay  Aorta;  N, 
cortical  substance  (in- 
terrenal  gland) ;  Uy 
ureter;  R,  rectum. 
Kohn. 


Anomalies. 

THE  KIDNEYS. — Rarely  is  there  congenital  absence  of  both  kidneys.  More 
often  there  is  a  high  degree  of  aplasia  in  both  organs  in  otherwise  well-developed 
children.  In  either  case  death  necessarily  soon  follows.  Not  infrequently  one 
kidney,  usually  the  left,  is  poorly  developed  or  absent  and  a  compensatory 
enlargement  of  the  other  exists.  Such  malformations  are  due  to  deficient 
development  of  the  organs,  but  the  causes  underlying  the  deficient  development 
are  obscure. 

One  of  the  most  common  malformations  is  the  abnormal  position  of  one  or 
both  kidneys  (ectopia  of  the  kidneys).  Usually  they  occupy  a  position  lower 
than  the  normal  in  the  abdominal  cavity,  which  indicates  that  they  have  failed, 
during  development,  to  migrate  forward  to  the  normal  limit  (see  p.  399).  Very 
rarely  one  or  both  organs  migrate  beyond  the  normal  limit,  in  which  case  they 
occupy  positions  cranial  to  the  normal. 

Not  infrequently  the  lower  ends  of  the  two  kidneys  are  fused  across  the 
medial  line,  giving  rise  to  the  so-called  "horseshoe  kidney."  Two  renal 
pelves  and  ureters  are  usually  present.  Occasionally  the  fusion  is  so  extensive 


430  TEXT-BOOK  OF  EMBRYOLOGY. 

that  a  single  flat  mass  is  formed.  This  occupies  a  medial  position  or  lies  at 
either  side  of  the  medial  line,  and  may  be  situated  at  the  normal  level  or  lower. 
The  renal  pelvis  may  be  single  or  double,  with  one  or  two  ureters.  In  cases  of 
double  ureters  and  pelves  it  seems  most  likely  that  the  anlagen  of  the  kidneys 
have  fused  secondarily,  that  is,  after  the  evagination  from  the  mesonephric 
ducts  (p.  391).  In  cases  where  the  pelvis  and  ureter  are  single,  the  fusion  may 
have  occurred  secondarily,  although  there  is  the  possibility  that  only  a  single 
anlage  appeared. 

Occasionally  in  children  and  even  in  adults  the  kidneys  show  a  distinct 
lobulation.  This  is  due  to  the  persistence  of  the  lobulation  that  normally 
exists  in  the  foetus  (p.  397). 

The  kidney  may  be  more  or  less  movable  owing  to  laxity  of  the  surrounding 
tissue,  or  it  may  be  floating,  in  which  case  it  has  a  distinct  mesentery.  These 
cases  should  be  distinguished  from  those  in  which  similar  conditions  have  been 
acquired,  usually  as  the  result  of  trauma. 

Congenital  cysts  of  the  kidney  are  not  uncommon.  They  vary  in  size  and 
number,  sometimes  being  so  numerous  that  they  crowd  out  the  greater  part 
of  the  renal  tissue.  Rarely  they  are  so  large  and  numerous  that  the  affected 
organ  fills  a  large  part  of  the  abdominal  cavity,  resulting  in  serious  or  even 
fatal  disturbances  of  the  functions  of  other  organs.  There  are  three  views  con- 
cerning the  origin  of  these  cysts,  (i)  They  may  be  the  result  of  dilatation  of 
certain  renal  tubules  derived  from  the  nephrogenic  tissue,  which  failed  to  unite 
with  the  straight  tubules  (p.  393).  (2)  Inflammation  in  the  medulla  of  the 
foetal  kidney  may  effect  a  closure  of  the  lumina  of  some  of  the  tubules,  with 
subsequent  dilatation  of  the  portions  (tubules  or  renal  corpuscles)  that  are  cut 
off  from  communication  with  the  renal  pelvis.  (3)  Normally  some  of  the  renal 
corpuscles  and  tubules  degenerate  (p.  399) ,  and  the  cysts  may  arise  as  dilatations 
of  incompletely  degenerated  corpuscles  or  tubules  or  both.  While  these  views 
appear  reasonable,  none  of  them  has  been  proven.  All  three  views  express 
possibilities,  and  there  is  no  good  reason  for  believing  that  any  one  of  them 
expresses  the  only  possibility. 

THE  URETERS. — The  renal  pelvis  is  sometimes  absent,  the  calyces  uniting 
to  form  two  or  more  tubes  which  in  turn  unite  to  form  the  ureter.  This  prob- 
ably is  the  result  of  abnormal  branching  of  the  ureter  during  development  and 
the  failure  of  the  ends  of  the  branches  to  become  dilated.  Occasionally  the 
ureter  is  double  or  triple  throughout  the  whole  or  a  part  of  its  length.  The 
most  reasonable  explanation  of  two  or  three  complete  ureters  on  either  side  is 
that  two  or  three  separate  evaginations  arose  from  the  mesonephric  duct  (p. 
391.)  Where  the  tube  is  double  in  only  a  part  of  its  length,  an  abnormal 
branching  of  the  single  original  evagination  is  indicated. 

Atresia  of  one  or  both  ureters  is  occasionally  met  with.     This  probably 


THE   DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  431 

represents  a  secondary  constriction  after  the  ureter  is  formed  since  both  evag- 
inations  are  hollow  from  the  beginning  (p.  391),  but  the  cause  of  the  constric- 
tion is  not  understood.  The  atresia  results  in  dilatation  of  the  portion  of  the 
ureter  on  the  side  toward  the  kidney. 

Abnormal  situations  of  the  openings  are  sometimes  seen,  the  explanation 
of  which  is  to  be  found  in  the  relations  of  these  tubes  to  the  mesonephric  ducts, 
to  the  cloaca,  and  to  the  Miillerian  ducts.  In  the  male  the  ureters  may  open  into 
the  seminal  vesicles,  the  prostatic  urethra,  or  the  rectum.  If  one  recalls  that 
the  ureter  arises  as  an  evagination  from  the  mesonephric  duct  near  the  opening 
of  the  latter  into  the  cloaca  (p.  391),  that  the  cloaca  becomes  separated  into  a 
dorsal  part  (the  rectum)  and  a  ventral  part  (the  urogenital  sinus)  (p.  400) ,  and 
that  the  proximal  end  of  the  mesonephric  duct  is  so  far  taken  up  into  the  wall 
of  the  urogenital  sinus  (or  bladder)  that  the  ureter  opens  separately  (p.  400),  it  is 
readily  seen  that  any  interference  with  these  normal  processes  of  development 
will  result  in  abnormal  opening  of  the  ureter.  If  the  ureter  does  not  become 
separated  from  the  mesonephric  duct,  it  will  open  into  the  deferent  duct  (vas 
deferens),  the  latter  being  the  proximal  part  of  the  mesonephric  duct.  And 
since  the  seminal  vesicle  is  an  outgrowth  from  the  proximal  end  of  the  meso- 
nephric duct,  the  opening  of  the  ureter  is  likely  to  be  associated  with  the  vesicle. 
If  the  separation  between  the  ureter  and  mesonephric  duct  is  complete,  but 
the  opening  of  the  ureter  does  not  migrate  cranially  on  the  wall  of  the  bladder, 
the  opening  comes  to  lie  in  the  wall  of  the  prostatic  urethra.  If  the  wall 
(urorectal  fold)  separating  the  urogenital  sinus  and  rectum  is  situated  too  far 
dorsally,  the  opening  of  the  ureter  comes  to  be  in  the  wall  of  the  rectum.  (Con- 
sult Figs.  360,  361,  362,  363.) 

In  the  female  the  ureters  may  open  into  the  urethra,  the  vagina,  or  the  uterus. 
The  explanation  of  the  opening  into  the  urethra  is  the  same  as  in  the  male 
(see  preceding  paragraph).  The  opening  into  the  genital  tract  is  probably  to 
be  explained  on  the  ground  that  the  ureters  fail  to  migrate  cranially  along 
the  wall  of  the  urogenital  sinus  to  the  bladder,  and  as  the  fused  ends  of  the 
Miillerian  ducts  enlarge  to  form  the  uterus  and  vagina,  the  openings  of  the 
ureters  are  taken  up  into  their  walls. 

THE  BLADDER. — Absence  of  the  bladder  is  very  rare.  Abnormal  small- 
ness,  due  to  imperfect  dilatation  of  the  urogenital  sinus  (p.  401),  is  not  infre- 
quent. 

The  urachus,  which  represents  the  portion  of  the  allantoic  duct  between 
the  bladder  and  the  umbilicus  (p.  401),  not  infrequently  persists  as  a  whole  or 
in  part,  giving  rise  to  certain  anomalous  conditions  in  the  region  of  the  middle 
umbilical  ligament.  The  urachus  may  persist  as  a  complete  tube,  lined 
with  epithelium,  thus  forming  a  means  by  which  urine  can  escape  at  the 
umbilicus.  This  condition  is  usually  associated  with  obstruction  of  the 


432  TEXT-BOOK  OF  EMBRYOLOGY. 

urethra  and  is  known  as  uracho-vesical  fistula.  The  urachus  may  degenerate 
in  part,  leaving  disconnected  portions  which  frequently  become  dilated  to 
form  cysts. 

Vesical  fissure,  the  most  serious  malformation  of  the  bladder,  is  associated 
with  fissure  of  the  lower  abdominal  wall.  The  edges  of  the  cleft  in  the  bladder 
are  continuous  with  those  of  the  cleft  in  abdominal  wall,  the  integument  being 
continuous  with  the  lining  of  the  bladder.  In  some  cases  the  bladder  is 
everted  through  the  cleft,  and  the  cleft  may  even  be  so  extensive  as  to  involve 
the  external  and  internal  genital  organs.  Vesical  fissure  is  much  more  com- 
mon in  the  male  than  in  the  female.  No  very  satisfactory  explanation  of  this 
malformation  has  yet  been  given.  It  is  in  some  way  connected  with  imperfect 
formation  of  the  ventral  abdominal  wall  resulting  from  influences  acting  at  a 
very  early  period  of  development. 

THE  URETHRA  in  both  sexes  may  be  abnormally  small  or  abnormally  large 
or  partly  occluded,  owing  to  faulty  development  of  the  urogenital  sinus.  In 
the  male  the  penile  portion  also  maybe  malformed,  being  represented  merely 
by  a  furrow  on  the  lower  side  of  the  penis.  This  condition,  known  as  hypo- 
spadias,  is  due  to  the  incomplete  fusion  or  lack  of  fusion  between  the  genital  folds 
along  the  lower  side  of  the  genital  tubercle  (p.  424) .  In  extreme  cases  the  de- 
fect may  involve  the  scrotum  and  extend  back  as  far  as  the  prostate  gland,  the 
two  halves  of  the  scrotum  being  separated.  Epispadias,  in  which  the  urethral 
cleft  extends  along  the  upper  side  of  the  penis  (or  the  clitoris)  is  rare,  and  is 
usually  associated  with  vesico-abdominal  fissure.  Its  mode  of  origin  is  not 
understood. 

THE  TESTICLES. — One  of  the  most  common  malformations  affecting  the 
male  genital  glands  is  the  condition  known  as  chryptorchism,  in  which  the 
glands,  instead  of  descending  into  the  scrotum,  are  retained  within  the  ab- 
dominal cavity.  One  or  both  testicles  may  be  affected.  They  may  occupy 
their  original  position  far  forward  in  the  abdominal  cavity  or  may  be  situated 
near  the  inguinal  canal,  or  may  lie  at  some  intermediate  point.  The  malposi- 
tion is  due  to  a  failure  in  the  normal  descent  into  the  scrotum  (p.  419).  The 
cause  of  the  failure  is  obscure.  Not  infrequently  the  ectopic  testicles  atrophy 
or  fail  to  develop  properly  at  puberty. 

Congenital  absence  of  one  or  both  testicles  is  rare.  More  frequently  the 
gland  or  efferent  system  of  ducts  is  defective  in  part,  owing  to  imperfect 
development.  In  case  of  absence  of  the  testicles  the  individual  is  small  and 
poorly  developed ;  when  the  glands  are  imperfectly  developed  the  individual  is 
effeminate. 

Cysts  which  are  sometimes  met  with  in  the  epididymis  are  possibly  due  to 
dilatation  of  incompletely  degenerated  portions  of  the  mesonephric  tubules 
or  Miillerian  ducts.  Teratoid  tumors  and  chorio-epitheliomata  are  occasionally 


THE  DEVELOPMENT  OF  THE  UROGENITAL  SYSTEM.  433 

found  in  the  testicle.  For  a  further  discussion  of  these  see  chapter  on  Terato- 
genesis  (XIX). 

THE  OVARIES. — Congenital  absence  of  both  ovaries  is  rare;  defective 
development  of  one  is  more  common.  Either  anomaly  may  occur  with  or 
without  defects  in  the  other  genital  organs.  Occasionally  the  ovaries  remain 
rudimentary,  their  function  as  egg-producing  organs  never  being  assumed. 
Malpositions,  due  to  partial  or  complete  failure  in  the  normal  descent  into 
the  pelvis  (p.  422),  are  not  infrequent.  Sometimes,  on  the  other  hand,  they 
descend  to  the  inguinal  canal  and  may  even  pass  through  the  latter  into  the 
labia  majora. 

Ovarian  cysts  occur  frequently.  Some  of  these  (follicular  cysts)  may  arise 
during  postnatal  life  as  dilatations  of  Graafian  follicles.  Others  probably 
arise  during  foetal  life  in  the  same  manner.  Certain  other  forms  of  ovarian 
tumors,  known  as  cystadenomata,  are  possibly  to  be  considered  as  derivatives 
of  the  epithelium  of  the  medullary  cords  which  in  normal  cases  disappear 
entirely  (p.  407;  also  Fig.  366).  A  discussion  of  the  origin  of  teratoid  tumors  of 
the  ovary  will  be  found  in  the  chapter  on  Teratogenesis  (XIX). 

THE  OVIDUCTS,  UTERUS  AND  VAGINA. — Absence  of  the  oviducts  is  usually 
associated  with  malformations  of  other  parts  of  the  genital  tract.  On  the  other 
hand,  normal  oviducts  may  be  present  in  conjunction  with  defective  uterus 
and  vagina.  Atresia  may  occur  at  the  uterine  or  fimbriated  end,  or  at  any 
intermediate  point. 

The  majority  of  the  malformations  of  the  uterus  and  vagina  can  be  at- 
tributed to  defective  processes  of  development  in  the  caudal  ends  of  the  Miiller- 
ian  ducts.  It  will  be  remembered  that  the  caudal  ends  of  these  ducts  normally 
fuse  to  form  a  single  medial  tube  which  opens  into  the  urogenital  sinus,  and 
which  constitutes  the  anlage  of  the  uterus  and  vagina  (p.  415;  Fig.  363).  It  is 
obvious  that  any  defect  in  this  fusion  will  result  in  some  degree  of  duplicity 
in  the  two  organs  in  question.  The  fusion  may  be  almost  complete,  the  result- 
ing abnormality  being  merely  a  small  pocket  which  forms,  at  each  side  of  the 
fundus,  a  continuation  of  the  cavity  of  the  uterus.  There  may  be  a  greater 
degree  of  imperfection  in  the  fusion,  resulting  in  a  partial  division  of  the  uterus 
into  two  horns — bicornuate  uterus.  The  wall  between  the  two  Miillerian  ducts 
may  remain  patent  in  the  entire  uterine  portion  of  the  tract,  thus  giving  rise 
to  a  bipartite  uterus.  If  the  wall  between  the  ducts  remains  intact  throughout 
both  uterine  and  vaginal  portions,  the  result  is  a  complete  division  of  the  utero- 
vaginal  tract — uterus  didelphys.  Occasionally  the  uterine  portion  of  one 
Miillerian  duct  may  fail  to  develop  properly  and  becomes  a  solid  cord,  resulting 
in  an  unicornuate  uterus. 

Not  infrequently  the  uterus  remains  rudimentary — infantile  uterus.  This 
anomaly  is  usually  accompanied  by  stenosis  of  the  vagina.  Stenosis  or  other 


434  TEXT-BOOK  OF  EMBRYOLOGY. 

defects  in  the  vagina  may  occur,  however,  when  the  uterus  is  normal.  In  rare 
instances  the  hymen  is  absent;  in  other  cases  it  closes  the  entrance  to  the  vagina 
• — a  condition  known  as  imperf orate  hymen. 

Malformations  of  the  uterus  and  vagina  resulting  from  persistence  of  the 
cloaca  and  atresia  of  the  anus  are  mentioned  on  page  357. 

HERMAPHRODITISM. 

This  condition  implies  a  combination  of  the  male  and  female  sexual  organs 
in  one  individual,  accompanied  by  a  blending  oi  the  general  characteristics  of 
the  two  sexes  When  such  an  individual  possesses  both  ovary  and  testicle,  the 
condition  is  known  as  true  hermaphroditism;  when  the  individual  possesses 
ovaries  or  testicles,  the  condition  is  known  as  false  hermaphroditism. 

TRUE  HERMAPHRODITISM. — The  presence  of  both  ovary  and  testicle  in  one 
individual  is  one  of  the  rarest  anomalies  in  man.  Furthermore,  one  or  both  of 
the  organs  are  sexually  immature.  Three  forms  can  be  recognized  (Klebs) : 

1.  Lateral  hermaphroditism,  in  which  an  ovary  is  present  on  one  side  and  a 
testicle  on  the  other; 

2.  Unilateral  hermaphroditism,  in  which  both  ovary  and  testicle  are  present 
on  one  side,  either  ovary  or  testicle,  or  neither,  on  the  other  side; 

3.  Bilateral  hermaphroditism,  in  which  both  ovary  and  testicle  are  present  on 
both  sides. 

In  all  these  cases  the  general  character  of  the  body  is  of  an  intermediate 
type,  sometimes  tending  toward  the  male,  sometimes  toward  the  female.  The 
external  genitalia  are  also  of  an  intermediate  type,  with  hypospadias,  small 
penis,  separate  scrotal  halves,  and  small  vaginal  orifice.  The  uterus  usually 
shows  some  degree  of  duplicity. 

FALSE  HERMAPHRODITISM. — In  this  type  of  hermaphroditism,  in  which 
either  ovaries  or  testicles  are  present  in  an  individual  with  mixed  general 
sexual  characteristics,  two  varieties  can  be  recognized : 

1.  Masculine  false  hermaphroditism,  the  more  common,  in  which  testicles  are 
present  but  the  external  genitalia  and  general  character  of  the  body  approximate 
the  female; 

2.  Feminine  false  hermaphroditism,  in  which  ovaries  are  present  but  other- 
wise male  characteristics  predominate. 

The  causes  underlying  the  origin  of  hermaphroditism  are  among  the  most 
obscure  in  teratogenesis.  It  is  well  known  that  up  to  the  fourth  or  fifth  week 
the  anlagen  of  the  sexual  glands  are  histologically  "indifferent,"  and  later  be- 
come differentiated  into  ovaries  or  testicles  (p.  405).  Since  the  secondary 
sexual  characteristics  are  dependent  upon  the  development  of  the  primary,  they 
also  are  brought  out  later.  If  the  "  indifferent "  glands  give  rise  to  both  ovaries 


THE  DEVELOPMENT  OF  THE   UROGENITAL  SYSTEM.  435 

and  testicles,  true  hermaphroditism  is  the  result;  if  they  give  rise  to  either 
ovaries  or  testicles  but  the  external  genitalia  and  general  characteristics  develop 
in  the  opposite  direction,  false  hermaphroditism  is  the  result.  Thus  the  her- 
maphroditic condition  is  potentially  present  in  every  individual  during  the 
earlier  stages  of  development;  the  most  remarkable  fact  is  that  it  is  not  more 
common. 

Recent  researches  in  cytology  have  added  a  new  phase  to  the  question  of  the 
origin  of  hermaphroditism.  Accessory  chromosomes  have  been  demonstrated 
in  the  ova  and  spermatozoa  of  many  species  of  insects  (McClung,  Wilson, 
Morgan)  and  in  ova  and  pollen  of  dioecious  plants  (Correns).  It  has  been 
suggested  that  these  have  some  significance  in  the  determination  of  sex,  the 
female  elements  containing  the  additional  chromatin  elements  (see  p.  27). 
Carrying  this  a  step  further,  Adami  has  suggested  that  "  hermaphroditism  is 
based  upon  aberration  in  the  distribution  of  the  chromosomes  in  either  the  ovum, 
or  the  spermatozoon." 

References  for  Further  Study. 

ADAMI,  J.  G.:  The  Principles  of  Pathology.     Vol.  I,  1908. 

AICHEL,  O.:  Vergleichende  Entwickelungsgeschichte  und  Stammesgeschichte  der 
Nebennieren.  Arch.  f.  mik.  Anat..  Bd.  LVL,  190x5. 

ALLEN,  B.  M.:  The  Embryonic  Development  of  the  Ovary  and  Testis  in  Mammals. 
Am.  Jour,  of  Anat.,  Vol.  Ill,  1904. 

BEARD,  J.:    The  Germ-cells  of  Prisdurus.     Anat.  Anz.,  Bd.  XXI,  1902. 

BEARD,  J.:  The  Morphological  Continuity  of  the  Germ  Cells  in  Raja  batis.  Anat.  Anz., 
Bd.  XVIII,  1900. 

BONNET,  R.:  Lehrbuch  der  Entwickelungsgeschichte.     Berlin,  1907. 

EIGENMANN,  C.  H.:  On  the  Precocious  Segregation  of  the  Sex-cells  of  Micrometrus 
aggregatus.  Jour  of  Morphol.,  Vol.  V,  1891. 

FELIX,  W.:  Entwickelungsgeschichte  des  Excretions-systems.  Ergebnisse  der  Anat. 
u.  Entwick.,  Bd.  XIII,  1903. 

FELIX,  W.,  and  BUHLER^  A.:  Die  Entwickelung  der  Harn-  und  Geschlechtsorgane.  In 
Hert wig's  Handbuch  d.  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  III. 
Teil  I,  1904. 

GAGE,  S.  P.:  A  Three  Weeks'  Human  Embryo,  with  Especial  Reference  to  the  Brain  and 
Nephric  System.  Am.  Jour,  of  Anat.,  Vol.  IV,  1905. 

GERHARDT,  U.:  Zur  Entwickelung  der  bleibenden  Nieren.     Arch.  f.  mik.  Anat ,  Bd 
ILVII,  1901 

HERTWIG,  O.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen  und  der  Wirbel- 
tiere. Jena,  1906. 

HILL,  E.  C.:  On  the  Gross  Development  and  Vascularization  of  the  Testis.  Am. 
Jour.  of.  Anat.,  Vol.  VI,  1907. 

HUBER,  G.  C.:  On  the  Development  and  Shape  of  the  Uriniferous  Tubules  of  Certain 
of  the  Higher  Mammals.  Am.  Jour,  of  Anat.,  Vol.  IV,  Suppl.,  1905. 

KEIBEL,  F.:  Zur  Entwickelungsgeschichte  des  menschlichen  Urogenitalapparatus. 
Arch.f.  Anat.  u.  Physiol.,  Anat.  Abth.y  1896. 

KOHN,  A.:  Das  chromaffine  Gewebe.    Ergebnisse  der  Anat.  u.  Entwick.,  Bd.  XII,  1903, 


436  TEXT-BOOK  OF  EMBRYOLOGY. 

KOLLMAX,  J.:  Lehrbuch  der  Entwickelungsgeschichte  des  Menschen.     Jena,  1898. 

KOLLMAX  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.  Jena,  1907, 
Bd.  II. 

M\RCHAXD,  F.:  Missbildungen.  In  Eulenburg's  Real-Encyclopadie  der  gesammten 
Heilkunde,  Bd.  XV,  1897. 

McMuRRiCH,  J.  P.:  The  Development  of  the  Human  Body.     Philadelphia,  1907. 

MIXOT,  C.  S.:  Laboratory  Text-book  of  Embryology.     Philadelphia,  1903. 

MORGAN,  T.  H.:  The  Cause  of  Gynandromorphism  in  Insects.  Am.  Xaturalist,  Vol. 
XLI,  1907. 

NAGEL,  W.:  Ueber  die  Entwickelung  des  Urogenitalsystems  des  Menschen.  Arch.  f. 
Mik.  Anal.,  Bd.  XXXIV,  1889. 

NAGEL,  W.:  Ueber  die  Entwickelung  der  Urethra  und  des  Dammes  beim  Menschen. 
Arch.f.  mik.  Anat.,  Bd.  XL,  1892. 

XAGEL,  W.:  U/eber  die  Entwickelung  des  Uterus  und  der  Vagina  beim  Menschen.  Arch. 
f.  mik.  Anat.,  Bd.  XXXVII,  1891. 

PIERSOL,  G.  A. :  Teratology.  In  Wood's  Reference  Handbook  of  the  Medical  Sciences, 
Vol.  VII,  1904. 

POLL,  H.:  Die  Entwickelung  der  Xebennierensysteme.  In  Hertwig's  Handbuch  der 
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RABL,  C.:  Ueber  die  Entwickelung  des  Urogenitalsystems  der  Selachier.  MarpJwl. 
Jahrbuch,  Bd.  XXFV,  1896.  Theorie  des  Mesoderms.  Ueber  die  erste  Entwickelung  der 
Keimdruse.  Morphol.  Jahrbuch,  Bd.  XXTV,  1896. 

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Zoologie,  Bd.  LXXI,  1902. 

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de  Biol.,  Paris,  Ser.  10,  T.  II,  1895. 

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superieurs.  Jour.  de.  FAnat.  et  de  la  Physiol.,  T.  XXXIX,  1903. 

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Anal.,  Vol.  I,  No.  3,  1902. 


CHAPTER  XVI. 
THE  DEVELOPMENT  OF  THE  IHTEGUMENTARY  SYSTEM. 

The  integument  consists  of  the  skin  and  certain  accessory  structures.  The 
skin  is  composed  of  the  dermis  (or  corium)  and  the  epidermis.  The  accessory 
structures  comprise  the  hairs,  nails,  sudoriferous  glands,  sebaceous  glands,  and 
mammary  glands.  The  epidermis  (or  epithelial  layer)  and  all  the  accessory 
structures  are  derived  from  the  ectoderm;  the  dermis  is  mesodermal  in  its 
origin.  Other  appendages  of  the  skin — such  as  scales,  feathers,  claws,  hoofs, 
and  horns — which  are  found  only  in  the  lower  animals,  are  ectodermal 
derivatives  and  belong  in  the  same  class  as  the  accessory  structures  in  man. 

The  Skin. 

THE  EPIDERMIS. — The  embryonic  ectoderm  consists  primarily  of  a  single 
layer  of  cells  (Fig.  81).  During  the  latter  part  of  the  first  month,  the  single 
layer  gives  rise  to  two  layers,  of  which  the  outer  is  composed  of  irregular  flat 
cells  and  is  known  as  the  epitrichium  or  periderm,  the  inner  or  basal,  of  larger 
cuboidal  cells  which  are  the  progenitors  of  the  epidermal  cells  and  of  the  acces- 
sory structures.  The  epitrichial  cells  later  become  dome-shaped  and  acquire 
a  vesicular  structure,'  the  nuclei  becoming  less  distinct.  They  persist  until  the 
middle  of  foetal  life  and  are  then  cast  off  and  mingle  with  the  secretion  of  the 

ly  formed  sebaceous  glands  as  a  constituent  of  the  vernix  caseosa  (see  p.  442) . 
The  epidermal  cells,  constantly  increasing  in  number,  soon  come  to  form  several 
layers  (4  to  6  in  the  sixth  month).  The  innermost  layer  rests  upon  the  base- 
ment membrane  and  is  composed  of  cuboidal  or  columnar  cells  rich  in  cytoplasm ; 
the  outer  layers  consist  of  irregular  cells  with  clearer  contents  and  less  distinct 
nuclei. 

As  development  proceeds,  the  basal  layer  gives  rise  to  several  layers  which 
together  constitute  the  stratum  germinativum.  The  cells  of  the  innermost 
layers  are  constantly  proliferating  and  thus  forming  new  cells  which  are  pushed 
toward  the  surface.  During  the  seventh  month  keratohyalin  granules  appear 
in  two  or  three  layers  which  are  then  known  collectively  as  the  stratum  granu- 
losum.  The  clearer  cells  of  the  superficial  layers  undergo  a  process  of  de- 
generation by  which  their  contents  are  transformed  into  a  horny  substance, 
the  nuclei  becoming  fainter  and  finally  disappearing.  These  modified  or  degen- 
erated cells,  which  are  constantly  being  cast  off  and  replaced  by  others  from 

437 


438  TEXT-BOOK  OF  EMBRYOLOGY. 

the  deeper  layers,  constitute  the  stratum  corneum  (Fig.  392).  In  the  thick 
epidermis,  on  the  palms  of  the  hands  and  the  soles  of  the  feet,  for  example,  a 
few  layers  of  cells  just  outside  of  the  stratum  granulosum  become  specially 
modified  (keratinized)  to  form  the  stratum  lucidum. 

THE  DERMIS. — In  the  first  month  the  dermis  is  represented  by  closely  ar- 
ranged, spindle-shaped  mesenchymal  (mesodermal)  cells  underlying  the 
epidermis,  and  is  separated  from  the  latter  by  a  delicate  basement  membrane. 
This  mesenchymal  tissue  gives  rise  to  fibrous  connective  tissue  which,  about 
the  third  month,  becomes  differentiated  into  two  layers — the  dermis  proper 
and  the  deeper  subcutaneous  tissue.  The  papillae  develop  as  little  projections 
of  the  dermis  which  grow  into  the  stratum  germinativum  of  the  epidermis. 
In  some  of  these,  many  blood  vessels  appear,  while  in  others  nerve  endings 

Eponychium 
Root  of  nail  Nail 


Sole  plate 


Phalanx  II 


Sweat  glands 

FIG.  391. — Longitudinal  section  through  the  end  of  the  middle  finger  of  a 
5  months  human  foetus.     Bonnet. 


(tactile  corpuscles  of  Meissner)  develop,  thus  giving  rise  to  vascular  and  nerve 
papillae.  Usually  a  considerable  amount  of  fat  develops  in  the  subcutaneous 
tissue.  Some  of  the  mesencnymal  cells  of  the  dermis  are  transformed  into 
smooth  muscle  cells  which  are  found  in  connection  with  the  hairs  (arrectores 
pilorum),  in  the  scrotum  (tunica  dartos),  and  in  the  nipples. 

The  dermis  has  generally  been  considered  as  a  derivative  of  the  cutis  plates 
(p.  163)  which,  with  the  myotomes,  constitute  the  outer  walls  of  the  primitive 
segments,  but  it  is  probable  that  the  outer  walls  of  the  segments  are  trans- 
formed wholly  into  muscle  tissue  (McMurrich). 

The  pigment  in  the  dermis  develops  in  the  form  of  granules  in  the  connect- 
ive tissue  cells;  that  in  the  epidermis  appears  as  granules  in  the  cells  of  the  deeper 
layers  (white  races)  or  of  all  the  layers  (dark  races).  Whether  the  pigment  in 
the  epidermis  arises  independently  or  is  carried  from  the  dermis  by  wandering 
cells  is  not  known. 


THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM.  439 

The  Nails. 

The  nails  are  derivatives  of  the  epidermal  layer  of  the  ectoderm,  and  cor- 
respond morphologically  to  the  claws  and  hoofs  of  lower  animals.  The 
epidermis  on  the  end  of  each  finger  and  toe  forms  a  thickening,  known  as  the 
primitive  nail,  which  is  encircled  by  a  faint  groove  (Zander).  This  occurs 
about  the  ninth  week.  Later  the  nail  area  migrates  to  the  dorsal  side  of  the 
digit  and  becomes  somewhat  sunken  below  the  surface  of  the  surrounding 
epithelium  (Fig.  391).  These  observations  have  led  to  the  conclusion  that 
primarily  the  nails  in  man  occupied  positions  on  the  ends  of  the  digits,  cor- 
responding to  the  positions  of  the  claws  in  lowrer  forms.  Furthermore,  the  fact 
that  the  nails  (or  their  anlagen)  are  at  first  situated  on  the  ends  of  the  digits  and 
subsequently  migrate  dorsally  would  exolain  the  innervation  of  the  nail  region 
by  the  palmar  (and  plantar)  nerves. 


Strat.  corneum  "I 

1  Epidermis 


#>        «    "     I     Strat.  germinativum  J 

/.-*I^ 

••  V-V  **: 

*i  I  Sf«SP@f- HairBerm 

(»*'         Hf Hair  papa 


papilla 

_-      i--,.^»  ,  w.w          -  », 


Con.  tis.  follicle 


Hair  germ 

Hair  papilla  Connective  tissue 

follicle 

FIG.  392. — Vertical  section  of  the  skin  of  a  mouse  embryo  of  18  mm.,  showing 
early  hair  germs.     Maurer. 

After  the  dorsal  migration  of  the  nail  area,  the  epithelium  and  dermis  along 
the  proximal  and  lateral  edges  become  still  more  elevated  to  form  the  nail  wall, 
the  furrow  between  the  latter  and  the  nail  being  the  nail  groove.  At  the  distal 
edge  of  the  nail  area,  the  epithelium  becomes  thickened  to  form  the  so-called 
sole  plate,  which  is  probably  homologous  with  the  more  highly  developed  sole 
plate  in  animals  with  hoofs  or  claws.  The  epithelium  of  the  nail  area  increases 
in  thickness,  and,  as  in  the  skin,  becomes  differentiated  into  three  layers 
(Fig.  391).  The  outer  layers  of  cells  become  transformed  into  the  stratum 
corneum.  The  cells  of  the  next  deeper  layers,  which  acquire  keratin  granules 
and  constitute  the  stratum  lucidum,  degenerate  and  give  rise  to  the  nail  sub- 
stance. Thus  the  nail  is  a  modified  portion  of  the  stratum  lucidum.  The 
layers  of  epithelium  beneath  the  nail  form  the  stratum  germinativum,  which, 
with  the  subjacent  dermis,  is  thrown  into  longitudinal  ridges. 


440  TEXT-BOOK  OF  EMBRYOLOGY. 

After  its  first  formation,  the  nail  is  covered  by  the  stratum  corneum  and 
the  epitrichium,  the  two  together  forming  the  eponychium.  The  epitrichium 
soon  disappears;  later  the  stratum  corneum  also  disappears  with  the  exception 
of  a  narrow  band  along  the  base  of  the  nail. 

The  formation  of  nail  substance  begins  during  the  third  or  fourth  month  in 
the  proximal  part  of  the  nail  area.  The  nail  grows  from  the  root  and  from  the 
under  surface  in  the  region  marked  by  the  whitish  color  (the  lumda).  New 
keratinized  cells  are  added  from  the  subjacent  stratum  germinativum  and  be- 
come degenerated  to  form  new  nail  substance  which  takes  the  place  of  the  old  as 
the  latter  grows  distally. 

The  Hair. 

The  hairs,  like  the  nails,  are  derivatives  of  the  epidermal  layer  of  the  ecto- 
derm. In  embryos  of  about  three  months,  local  thickenings  of  the  epidermis 
appear  (beginning  in  the  region  of  the  forehead  and  eye-brows)  and  grow 
obliquely  into  the  underlying  dermis  in  the  form  of  solid  buds — the  hair  germs 
(Fig.  393,  I,  II).  As  the  buds  continue  to  elongate  they  become  club-shaped 
and  the  epithelium  at  the  end  of  each  molds  itself  over  a  little  portion  of  the 
dermis  in  which  the  cells  have  become  more  numerous  and  which  is  known  as 
the  hair  papilla  (Fig.  392). 

As  the  epidermal  bud  grows  deeper,  its  central  cells  become  spindle-shaped 
and  undergo  keratinization  to  form  the  beginning  of  the  hair  shaft;  the  peripheral 
layers  constitute  the  anlage  of  the  root  sheath  (Fig.  393,  III,  IV).  The  hair 
shaft  grows  from  its  basal  end,  new  keratinized  cells  being  added  from  the 
epithelium  nearest  the  papilla  as  the  older  cells  are  pushed  toward  the  surface 
of  the  skin.  The  surface  cells  of  the  hair  shaft  become  flattened  to  form  the 
cuticle  of  the  hair  (Fig.  393,  V).  The  hairs  appear  above  the  surface  about  the 
fifth  month.  Of  the  cells  of  the  root  sheath,  those  nearest  the  hair  become 
scale-like  to  form  the  cuticle  of  the  root  sheath;  the  next  few  layers  become 
modified  (keratinized)  to  form  Huxley's  and  Henle's  layers.  Outside  of  these 
is  the  stratum  germinativum,  the  basal  layer  of  which  is  composed  of  columnar 
cells  resting  upon  a  distinct  basement  membrane.  The  stratum  germinativum 
is  continued  over  the  tip  of  the  papilla,  where  its  cells  give  rise  to  new  cells  for 
the  hair  shaft  (Fig.  393,  V). 

The  connective  tissue  around  the  root  sheath  becomes  differentiated  into  an 
inner  highly  vascular  layer,  the  fibers  of  which  run  circularly,  and  an  outer 
layer,  the  fibers  of  which  extend  along  the  sheath.  The  two  layers  together  con- 
stitute the  connective  tissue  follicle. 

The  first  formed  hairs,  which  are  exceedingly  fine  and  silky,  develop  in  vast 
numbers  over  the  surface  of  the  embryonic  body  and  are  known  collectively  as 
the  lanugo.  This  growth  is  lost  (beginning  before  birth  and  continuing  during 


THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM. 


441 


the  first  and  second  years  after),  except  over  the  face,  and  is  replaced  by  coarser 
hairs.     These  in  turn  are  constantly  being  shed  during  the  life  of  the  individual 

t 


0 


\   ^m^7     MM 


\^^p^r      ^m 

ls^*&*£  i 

£>Vf         tr<-2&?  :***f&     ••'<< 

^  ft 


FIG.  393. — Five  stages  in  the  development  of  a  human  hair. 
C,  Papilla;    5,  arrector  pili  muscle;   c,  beginning  of  hair  shaft;  d,  point  where  hair  shaft  grows 
through  epidermis;   e,  anlage  of  sebaceous  gland;   /,  hair  germ;  g,  hair  shaft;    h,  Henle's 
layer;  «,  Huxley's  layer;  k,  cuticle  of  root  sheath;  /,  inner  root  sheath;  m,  outer  root  sheath 
in  tangential  section;  n,  outer  root  sheath;  o,  connective  tissue  follicle. 

and  replaced  by  new  ones.     The  new  hairs  probably  in  most  cases  develop  from 
the  old  follicles,  the  cells  over  the  old  papillae  proliferating  and  the  newly 


442  TEXT-BOOK  OF  EMBRYOLOGY. 

formed  hairs  growing  up  through  the  old  sheaths.  In  some  cases,  however,  new 
follicles  are  formed  directly  from  the  epidermis  and  dermis.  In  some  of  the 
lower  Mammals,  new  hair  germs  appear  as  outgrows  from  the  sheaths  of  old 
follicles,  thus  giving  rise  to  tufts  of  hair.  The  arrectores  pilorum  muscles  arise 
from  the  dermal  (mesenchymal)  cells  and  become  attached  to  the  follicles  below 
the  sebaceous  glands. 

The  Glands  of  the  Skin. 

THE  SEBACEOUS  GLANDS. — These  structures  usually  develop  in  connection 
with  hairs.  From  the  root  sheath  a  solid  bud  of  cells  grows  out  into  the  dermis 
(Fig.  393,  IV)  and  becomes  lobed.  The  central  cells  of  the  mass  undergo  fatty 
degeneration  and  the  products  of  degeneration  pass  to  the  surface  of  the  skin 
through  the  space  between  the  hair  and  its  root  sheath.  The  more  peripheral 
cells  proliferate  and  give  rise  to  new  central  cells  which  in  turn  are  transformed 
into  the  specific  secretion  of  the  gland,  the  whole  process  being  continuous.  On 
the  margins  of  the  lips,  on  the  labia  minora  and  on  the  glans  penis  and  prepuce, 
glands  similar  in  character  to  the  sebaceous  glands  arise  directly  from  the 
epidermis  independently  of  hairs. 

THE  SUDORIFEROUS  GLANDS. — The  sweat  glands  begin  to  develop  during 
the  fifth  month  as  solid  cylindrical  growths  from  the  deeper  layers  of  the  epider- 
mis into  the  dermis  (Fig.  391).  Later  the  deeper  ends  of  the  cylinders  become 
coiled  and  lumina  appear.  The  lumina  do  not  at  first  open  upon  the  surface 
but  gradually  approach  it  as  the  deeper  epidermal  layers  replace  the  more 
superficial. 

THE  VERNIX  CASEOSA. — During  fcetal  life  the  secretion  of  the  sebaceous 
glands  becomes  mingled  with  the  cast-off  epitrichial  and  epidermal  cells  to  form 
the  whitish  oleaginous  substance  (sometimes  called  the  smegma  embryonum) 
that  covers  the  skin  of  the  new-born  child.  It  is  collected  especially  in  the 
axilla,  groin  and  folds  of  the  neck. 

THE  MAMMARY  GLANDS. 

In  embryos  of  six  to  seven  mm.,  or  even  less,  a  thickening  of  the  epidermis 
occurs  in  a  narrow  zone  along  the  ventro-lateral  surface  of  the  body  (Strahl). 
In  embryos  of  1 5  mm.  this  thickening,  known  as  the  milk  ridge,  extends  from  the 
upper  extremity  to  the  inguinal  region  (Kallius,  Schmidt).  Later  the  caudal 
end  of  the  ridge  disappears,  while  the  cephalic  portion  becomes  more  prominent. 
The  further  history  of  the  ridge  has  not  been  traced,  but  in  embryos  considerably 
older  the  anlage  of  each  gland  is  a  circular  thickening  of  the  epidermis  in  the 
thoracic  region,  projecting  into  the  underlying  dermis.  It  seems  most  probable 
that  this  local  thickening  represents  a  portion  of  the  original  ridge,  the  remainder 


THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM.  443 

having  disappeared.  Later  the  central  cells  of  the  epidermal  mass  become 
cornified  and  are  cast  off,  leaving  a  depression  in  the  skin  (Fig.  394).  In  em- 
bryos of  250  mm.  a  number  of  Solid  secondary  buds  have  grown  out  (Fig.  395). 
These  resemble  the  anlagen  of  the  sweat  glands,  to  which  they  are  generally 
considered  as  closely  allied  (Hertwig,  Wiedersheim  and  others), and  represent 
the  excretory  ducts.  Continued  evaginations  from  the  terminal  parts  of  the 
excretory  ducts  form  the  lobular  ducts  and  acini.  The  acini,  however,  are 
scarcely  demonstrable  in  the  male,  and  not  even  in  the  female  until  pregnancy. 
Lumina  appear  by  a  separation  and  breaking  down  of  the  central  cells  of  the 
ducts  and  acini,  the  peripheral  cells  remaining  as  their  lining. 

Nipple 
Epitrichium  depression  Dermis 


Stratum 
germinativura 


Dermis 
(Areolar  zone) 


Vv  v:.v  -. '  ^  ?5«a!S3?sgES#S  -  *     '• " 


FIG.  394. — Vertical  section  through  the  anlage  of  the  mammary  gland  of 
a  human  foetus  of  16  cm.     Bonnet. 

Late  in  foetal  life,  or  sometimes  after  birth,  the  original  depressed  gland 
area  becomes  elevated  above  the  surface  to  form  the  nipple.  The  excretory 
ducts  (15  to  20  in  number)  which  at  first  opened  into  the  depression,  thus  come 
to  open  on  the  surface  of  the  nipple.  In  the  area  around  the  nipple — the 
areola — numerous  sudoriferous  and  sebaceous  glands  develop,  some  of  which 
come  to  open  into  the  lacteal  ducts.  Sometimes  rudimentary  hairs  appear. 
Other  glands — known  as  areolar  glands  (of  Montgomery) — resembling  rudi- 
mentary mammary  glands  also  develop  from  the  epidermis  of  the  areola. 

After  birth  the  mammary  glands  continue  to  grow  slowly  in  both  sexes  up  to 
the  time  of  puberty.  After  this  they  cease  to  grow  in  the  male,  and  then  atrophy. 
In  the  female,  growth  of  the  glandular  elements  goes  on,  but  very  slowly,  and 
usually  a  considerable  amount  of  fat  develops  in  the  surrounding  tissue, 
causing  the  enlargement  of  the  breasts. 

The  Mammary  Glands  of  Pregnancy. — Even  in  the  female,  as  stated  before, 
acini  are  scarcely  demonstrable  until  pregnancy.  The  mamma  consists 


444 


TEXT-BOOK  OF  EMBRYOLOGY. 


mostly  of  connective  tissue  and  fat,  with  scattered  groups  of  duct-like  tubules. 
During  pregnancy  the  tubules  give  rise  to  the  acini  by  a  process  of  evagination, 
the  cells  increasing  in  number  by  mitosis.  Toward  the  end  of  pregnancy  each 
excretory  duct  and  its  smaller  ducts  and  acini  form  a  distinct  lobe  with  a  rela- 
tively small  amount  of  connective  tissue.  The  epithelium  is  low  or  cuboidal, 
and  fat  begins  to  accumulate,  in  the  seventh  or  eighth  month,  as  droplets  in  the 
basal  parts  of  the  cells.  The  droplets  increase  in  number  and  in  size,  approach- 
ing the  inner  end  of  the  cell,  until  finally  the  cell  is  practically  filled.  At  the 
beginning  of  lactation  the  fat  escapes  into  the  lumen  of  the  acinus,  leaving  a  bit 
of  ragged  cytoplasm  with  a  nucleus.  This  regenerates  into  a  cell  capable  of 


Stroma 
(dermis) 


Stroma 


FIG.  395.  —  Vertical  section  of  the  anlage  of  the  mammary  gland  of  a  human  foetus  of  25  cm.    Nagel. 


further  activity;  and  it  is  probable  that  the  same  cell  may  become  filled  with 
fat  and  discharge  its  contents  several  times  during  lactation. 

During  pregnancy  and  lactation  the  acini  also  contain  leucocytes  which  have 
wandered  through  the  epithelium  from  the  surrounding  tissue.  These  contain 
fat  droplets  and  are  known  as  colostrum  corpuscles. 

At  the  end  of  lactation  the  acini  atrophy  and  disappear,  the  lobules  becoming 
masses  of  connective  tissue  and  fat,  which  contain  groups  of  duct-like  tubules 
and  which  are  so  closely  joined  with  one  another  that  they  are  indistinguishable 
as  lobules. 

'  Anomalies. 

ANOMALIES  or  THE  SKIN. — The  epidermis  may  develop  to  an  abnormal  de- 
gree over  the  entire  surface  of  the  body,  forming  a  horny  layer  which  is  broken 
only  where  the  skin  is  folded  by  the  movement  of  the  members  of  the  body— 
a  condition  known  as  hyperkeratosis.  Or  the  abnormal  development  may  give 
rise  to  irregular  patches  of  thick  epithelium — ichihyosis.  In  either  case,  hairs 
and  sebaceous  glands  are  usually  absent  over  the  affected  areas. 


THE  DEVELOPMENT  OF  THE  INTEGUMENTARY  SYSTEM.  445 

Occasionally  pigment  develops  in  excess  over  larger  or  smaller  areas  of  the 
skin,  giving  rise  to  the  so-called  navi  pigmentosi.  In  some  cases,  on  the  other 
hand,  there  is  total  or  almost  total  lack  of  pigment  in  the  skin  and  hair  (usually 
accompanied  by  defective  pigmentation  of  the  iris,  chorioid  and  retina) — • 
a  condition  known  as  albinism.  There  are  also  instances  of  partial  albinism. 
The  influence  of  heredity  in  albinism  is  doubtful,  for  albinos  are  usually  the 
children  of  ordinary  parents. 

The  angiomata  (lymphangiomata,  haemangiomata)  found  in  the  skin  are  due 
to  dilated  lymphatic  or  blood  channels,  the  color  in  haemangiomata  being  due 
to  the  haemoglobin  in  the  blood. 

Dermoid  Cysts. — The  congenital  dermoid  cysts  not  infrequently  found  in  or 
under  the  skin  are  usually  situated  in  or  near  the  line  of  fusion  of  embryonic 
structures,  as  in  the  region  of  the  branchial  arches,  along  the  ventral  body 
wall  and  on  the  back.  During  the  fusion  of  adjacent  structures,  portions  of  the 
epidermis  become  constricted  from  the  parent  tissue  and  come  to  lie  in  the  der- 
mis,  where  they  continue  to  grow  and  produce  cystic  masses  and  sometimes 
give  rise  to  hairs  and  sebaceous  glands.  This  type  of  dermoid  is  to  be  dis- 
tinguished from  that  found  for  example  in  the  ovary,  in  which  derivatives  of 
all  three  germ  layers  are  present  (see  Chap.  XIX). 

ANOMALIES  OF  THE  EPIDERMAL  DERIVATIVES. — Occasionally  hair  develops 
in  profusion  over  areas  of  the  skin  that  naturally  possess  only  a  fine,  silky  growth, 
such,  for  example,  as  a  woman's  face.  Or  nearly  the  entire  body  may  be 
covered  by  an  unusual  amount  of  hair.  Such  conditions — known  as  hyper- 
trichosis — possibly  represent  the  persistence  and  continued  growth  of  the 
lanugo  (p.  440)  and  in  this  sense  are  to  be  regarded  as  the  result  of  arrested 
development  (Unna,  Brandt).  Congenital  absence  of  the  hair  (hypotrichosis, 
alopecia)  is  a  rare  anomaly  and  is  usually  accompanied  by  defective  develop- 
ment of  the  teeth  and  nails. 

Sebaceous  cysts,  generally  regarded  as  due  to  accumulation  of  secretion 
in  the  sebaceous  glands,  sometimes  probably  represent  remnants  of  displaced 
pieces  of  epidermis  apart  from  the  hairs  (Chiari) . 

Supernumerary  mammary  glands  (hypermastia)  and  nipples  (hyperthelia)  are 
not  infrequently  present  in  both  males  and  females.  They  are  usually  situated 
below  the  normal  mammae  (rarely  in  the  axillary  region) ,  in  a  line  drawn  from 
the  axilla  to  the  groin,  and  probably  represent  persistent  and  abnormally  de- 
veloped portions  of  the  milk  ridge  (see  p.  442)  In  very  rare  cases  a  super- 
numerary gland  develops  in  some  other  region  (even  on  the  thigh) .  If  the 
mammary  glands  are  morphologically  allied  to  the  sweat  glands  (p.  443),  these 
misplaced  mammae  are  suggestive  of  anomalous  development  of  some  of  the 
sweat  gland  anlagen. 


446  TEXT-BOOK  OF  EMBRYOLOGY. 

References  for  Further  Study. 

BROUHA:  Recherches  sur  les  di verses  phases  du  developpement  et  de  1'activite  de  la 
mammelle.     Arch,  de  BioL,  T.  XXI,  1905. 

BONNET,  R.:  Die  Mammarorgane  im  Lichte  der  Ontogenie  und  Phylogenie.     Ergebnisse 
d.  Anat.  u.  Entwick.,  Bd.  II,  1892;  Bd.  VII,  1898. 

KALLIUS,  E.:  Ein  Fall  von  Milchleiste  bei  einem  menschlichen  Embryo.     Anat.  Hefte, 
Bd.  VIII,  1897. 

KEIBEL,  F.,  and  MALL,  F.  P.:  Manual  of  Human  Embryology,  Vol.  I,  1910. 

KRAUSE,   W.:  Die   Entwickelung   der   Haut   und   ihrer   Nebenorgane.     In   Hertwig's 
Handbuch  d.  vergleich.  u.  experiment.  Entwick elungslehre  der  Wirbeltiere,  Bd.  II,  Teil  I,  1902. 

OKAMURA,  T.:  Ueber  die  Entwickelung  des  Nagels  beim  Menschen.     Arch.  /.  Der- 
matol.  u.  Syphilol.,  Bd.  XXV,  1900. 

PIERSOL,  G.  A. :  Teratology.     In  Wood's  Reference  Handbook  of  the  Medical  Sciences, 
Vol.  VII,  1904. 

SCHMIDT,  H.:   Ueber    normale   Hyperthelie  menschlicher   Embryonen   und   tiber    die 
erste  Anlage  der  menschlichen  MilchdrUsen  iiberhaupt.     Morphol.  Arbeiten,  Bd.  XVII,  1897. 

SCHULTZE,  O.:  Ueber  die  erste  Anlage  des  MilchdrUsen  Apparates.     Anat.  Anz.,  Bd. 
VIII,  1892. 

STOHR,    P.:  Entwiokelungsgeschichte    des    menschlichen    Wollhaares.     Anat.    Hefte, 
Bd.  XXIII,  1903. 

STRAHL,  H.:  Die  erste  Entwickelung  der  Mammarorgane  beim  Menschen.     Verhandl. 
d.  Anat.  Gesellsch.,  Bd.  XII,  1898. 

ZANDER,  R.:  Bie  friihesten  Stadien  der  Nagelentwickelung  und   ihre  Beziehungen  zu 
den  Digitalnerven.     Arch.  f.  Anat.  u.  Physiol.,  Anat.  Abth.,  1884. 


CHAPTER  XVII. 
THE  NERVOUS  SYSTEM. 

BY  OLIVER  S.   STRONG. 
GENERAL  CONSIDERATIONS. 

There  are  certain  features  of  the  nervous  system  in  general  and  particularly 
of  the  vertebrate  nervous  system,  the  comprehension  of  which  makes  the 
processes  of  development  of  the  nervous  system  in  man  more  intelligible. 
First,  the  nervous  systems  of  the  lower  Vertebrates  are  in  many  respects 
simpler  than  those  of  higher  forms  and  their  variations  throw  light  upon  the 
causes  which  determine  neural  structures.  Second,  as  the  nervous  systems  of 
all  Vertebrates  develop  from  the  same  germ  plasm,  there  are  resemblances 
between  certain  features  of  both  the  embryonic  and  adult  systems  of  lower 
vertebrates  and  certain  developmental  stages  in  the  higher.  Certain  struc- 
tures met  with  in  lower  adult  forms  may  be  regarded  as  representing  stages 
of  arrested  development — although  specialized  and  aberrant  in  many  respects 
— of  structures  found  in  higher  forms.  Vestigial  structures  in  the  developing 
nervous  systems  of  higher  forms  may  be  regarded  as  recurring  developmental 
necessities  in  the  attainment  of  the  adult  form. 

Stated  in  the  most  general  terms,  coordination  of  bodily  activities  in  response 
to  both  external  and  internal  conditions  is  the  biological  significance  of  the 
nervous  system.  This  implies  a  transmission  of  some  form  of  change  from  one 
part  to  another  or,  in  other  words,  conduction.  This  functional  necessity  is 
shown  structurally  in  the  elongated  form  of  the  histological  elements  of  the 
nervous  system.  That  such  changes  habitually  pass  along  each  element  or 
neurone  in  some  one  direction  seems  to  find  a  natural  structural  expression  in 
the  receptive  body  and  dendrites  of  the  neurone,  and  in  its  long  transmitting 
axone. 

It  is  also  evident  that  coordination  can  only  be  performed  by  a  transmission 
of  a  change  from  some  given  structure  either  back  to  that  structure  or  to  some 
other  structure  to  cause  a  responsive  change.  We  thus  have  not  only  in  the 
vertebrate,  but  at  a  very  early  stage  in  the  invertebrate  nervous  system,  a  dif- 
ferentiation into  afferent  and  efferent  components,  the  two  together  usually 
being  termed  the  peripheral  nervous  system.  The  histological  elements  of  these 
components  are  the  afferent  and  efferent  peripheral  neurones.  All  structures 
which  are  so  affected  as  to  transmit  the  change  to  the  afferent  peripheral  neu- 

447 


448 


TEXT-BOOK  OF  EMBRYOLOGY. 


rones  may  be  conveniently  termed  receptors,  those  structures  affected  by  the 
efferent  peripheral  neurones  may  be  termed  effectors  (Sherrington).  Receptors 
include  various  "sensory"  structures  whose  principal  function  appears  to  be 
to  limit  to  some  particular  kind  of  stimulus  the  changes  affecting  the  afferent 
nervous  elements  connected  with  them.  Effectors  include  various  structures 
(muscles,  glandular  epithelia)  whose  activities  are  influenced  by  the  nervous 
system  (Fig.  396).  A  primitive  nervous  mechanism,  thus  composed  of  (i) 
afferent  peripheral  neurones  which  transmit  the  stimulus  from  a  receptor  to 
(2)  efferent  peripheral  neurones  which  in  turn  transmit  the  stimulus  to  an 
effector,  is  a  simple,  two-neurone  reflex  arc  (Fig.  396). 

At  the  same  time  these  neurones,  as  they  increase  in  number,  are  obviously 
brought  into  relation  with  each  other  with  more  economy  of  space  by  having 


Receptor 


Effector 


FIG.  396. — A  two-neurone  reflex  arc  in  a  Vertebrate,     gg..  Ganglion,     van  Gehuchten* 

common  meeting  places.  This,  together  with  the  factor  noted  below,  leads  to 
the  concentration  of  an  originally  diffuse  nervous  system,  spread  out  principally 
in  connection  with  the  outer  (ectodermal)  surface,  into  a  more  centralized 
(ganglionic)  type  of  nervous  system,  which  at  the  same  time  has  in  part  re- 
treated from  the  surface  layer  (ectoderm)  from  which  it  was  originally  derived 

(Fig.  397)- 

Furthermore,  when  we  consider  the  great  number  of  receptors  and  effectors 
in  even  simple  forms,  it  is  apparent  that  for  effective  coordination  there  must  be 
a  considerable  degree  of  complexity  of  association  between  the  afferent  and 
efferent  neurones.  These  associations  may  be  to  some  extent  accomplished  by 
various  branches  of  the  afferent  and  efferent  neurones  coming  directly  into 
various  relations  with  each  other,  but  it  is  also  evident  that  when  a  certain 


THE  NERVOUS  SYSTEM. 


449 


degree  of  complexity  is  reached,  such  an  arrangement  would  necessitate  an 
extraordinary  number  of  afferent  and  efferent  neurones  or  an  extraordinary 
development  of  branches  of  each  where  they  connect.  Accordingly  we  find  a 
second  category  of  neurones,  the  intermediate  or  central  neurones  which  mediate 


Lumbricus 


Nereis. 


Vertebrata 


FIG.  397. — Illustrating  the  withdrawal  from  the  surface  of  the  bodies 
of  the  afferent  peripheral  neurones.     After  Retzius. 

between  the  afferent  and  efferent  peripheral  neurones.  These  central  neurones, 
together  with  portions  of  peripheral  neurones  in  immediate  relation  with  them, 
form,  in  all  fairly  well  differentiated  nervous  systems,  including  those  of  all 
Vertebrates,  the  central  as  distinguished  from  the  peripheral  nervous  system. 


FIG.  398. — A  three-neurone  reflex  arc.     van  Gehuchten. 
I,  Afferent  peripheral  neurone;  2,  intermediate  or  central  neurone;  3,  efferent  peripheral  neurones. 

The  change  or  stimulus  would  now  pass  from  receptor  through  (i)  afferent 
peripheral  neurones,  (2)  intermediate  neurones,  (3)  efferent  peripheral  neu- 
rones to  effector.  This  arrangement  constitutes  a  three-neurone  reflex  arc 


450  TEXT-BOOK  OF  EMBRYOLOGY. 

(Fig.  398),  and  is  evidently  capable  of  complicated  combinations  which  may 
be  further  increased  in  complexity  by  the  intercalation  in  the  arc  of  other 
intermediate  neurones.  Finally,  in  the  central  nervous  system  certain  struc- 
tures consisting  of  intermediate  neurones  are  developed  which  represent  the 
mechanisms  for  certain  coordinations  of  the  highest  order.  Such  are  the 
higher  coordinating  centers  (suprasegmental  structures  of  Adolf  Meyer) . 

As  a  result  of  the  preceding,  it  follows  that  in  seeking  the  explanation  for 
various  nervous  structures  there  must  always  be  kept  in  mind,  first,  their  correla- 
tion with  peripheral  structures  and,  second,  the  degree  of  development  of  the 
central  coordinating  mechanism  represented  by  the  intermediate  or  central 
neurones.  The  most  important  features  common  to  the  nervous  systems  of 
all  Vertebrates  owe  their  uniformity  either  to  a  corresponding  uniformity  in 
the  peripheral  receptors  and  effectors,  or  to  a  uniformity  in  the  coordinations  of 
the  stimuli  received  and  given  out  by  the  central  nervous  system.  Variations 
in  structure  are  due  to  variations  of  either  the  peripheral  or  central  factor  above 
mentioned.  In  the  lower  Vertebrates  the  former  factor  plays  a  relatively  more 
important  part  than  in  the  higher  Vertebrates,  the  central  apparatus  being 
simpler;  while  in  the  development  of  the  higher  vertebrate  nervous  systems  the 
dominating  factor  is  the  increasing  complexity  of  the  central  mechanism.  The 
superiority  of  the  nervous  system  of  man  does  not  consist,  in  the  main,  of  supe- 
riority in  sense  organs  or  motor  apparatus,  but  in  the  enormous  development  of 
the  intermediate  neurone  system. 

GENERAL  PLAN  OF  THE  VERTEBRATE  NERVOUS  SYSTEM. 

The  Vertebrate  is  an  elongated  bilaterally  symmetrical  animal  progressing 
in  a  definite  direction,  primitively  perhaps  by  alternating  lateral  contractions 
performed  by  a  segmented  lateral  musculature.  Associated  with  these  char- 
acteristics are  the  bilateral  character  of  the  nervous  system  and  its  transverse 
segmentation,  shown  by  its  series  of  nerves,  a  pair  to  each  muscle  segment. 
The  definite  direction  of  progression  involves  a  differentiation  of  the  forward 
extremity  of  the  animal,  such  as  the  location  there  of  the  mouth  and  respiratory 
apparatus  and  the  development  there  of  specialized  sense  organs,  the  nose,  eye, 
ear,  lateral  line  organs,  and  taste  buds,  which  increase  the  range  of  stimuli 
received  by  the  animal  and  thereby  render  possible  a  greater  range  of  responsive 
activities  in  obtaining  food  and  in  reproduction.  As  a  natural  outgrowth 
of  these  specializations,  the  highest  development  of  the  central  coordinating 
mechanism  also  takes  place  at  the  forward  end  or  head.  This  concentration 
and  development  of  various  mechanisms  in  the  anterior  end  is  usually  termed 
cephalization,  and  is  a  tendency  exhibited  also  by  various  groups  of  Inverte- 
brates in  which  the  same  general  conditions  are  present. 

The  typical  vertebrate  nervous  system,  then,  consists  of  a  bilateral  central 


THE  NERVOUS  SYSTEM.  451 

nervous  system  connected  by  means  of  a  series  of  segmental  nerves  with  per- 
ipheral structures  (receptors  and  effectors)  and  exhibiting  at  its  anterior  ex- 
tremity a  higher  development  .and  specialization  in  both  its  peripheral  and 
central  parts. 

The  general  features  of  the  typical  vertebrate  nervous  system  are  best 
revealed  by  a  brief  examination  of  certain  stages  in  its  development. 

The  entire  nervous  system,  except  the  olfactory  epithelium  and  parts  of 
certain  ganglia  (see  p.  452),  is  derived  ontogenetically  from  an  elongafed  plate 
of  thickened  ectoderm,  the  neural  plate.  This  plate  extends  longitudinally  in 
the  axis  of  the  developing  embryo,  its  position  being  usually  first  indicated 
externally  by  a  median  groove,  the  neural  groove  (Fig.  410),  the  edges  of  the 
plate  being  elevated  into  the  neural  folds  (Fig.  411).  The  neural  folds  are 
continuous  around  the  cephalic  end  of  the  plate,  but  diverge  at  the  caudal 
end,  enclosing  between  them  in  this  region  the  blastopore.  Even  at  this  stage, 
the  neural  plate  is  usually  broader  at  its  cephalic  end,  thereby  indicating  already 
the  future  differentiation  into  brain  and  spinal  cord  (Fig.  413).  The  neural 
folds  now  become  more  and  more  elevated  (Fig.  412),  presumably  due  in 
part  to  the  growth  of  the  whole  neural  plate,  and  finally  meet  dorsally  and  fuse, 
thus  forming  the  neural  tube  (Figs.  72  and  429).  The  fusion  of  the  lips  of  the 
neural  plate  to  form  the  neural  tube  usually  begins  somewhere  in  the  middle 
region  of  the  plate  and  thence  proceeds  both  forward  and  backward  (Fig.  119). 
The  last  point  to  close  anteriorly  is  usually  considered  as  marking  the  cephalic 
extremity  of  the  neural  tube,  and  is  called  the  anterior  neuropore. 

Even  before  the  neural  plate  closes  to  form  the  tube,  there  is  often  a  differen- 
tiation of  cells  along  each  edge,  forming  an  intermediate  zone  between  the 
neural  plate  and  the  non-neural  ectoderm  (Fig.  429).  As  the  neural  plate 
becomes  folded  dorsally  into  the  neural  tube  these  two  zones  are  naturally 
brought  together  at  the  point  of  fusion  of  the  dorsal  lips  of  the  neural  plate. 
The  two  zones  thus  brought  together  are  not  included  in  the  wall  of  the  neural 
tube,  but  form  a  paired  or  unpaired  ridge  of  cells  lying  along  its  dorsal  surface. 
This  ridge  of  cells  is  called  the  neural  crest  (Fig.  429).  Later,  each  half  of  the 
neural  crest  separates  from  the  other  half  and  from  the  neural  tube  and  passes 
ventrally  down  along  the  sides  of  the  tube,  at  the  same  time  becoming  trans- 
versely divided  into  blocks  of  cells  (Fig.  434).  These  masses  of  cells  are  the 
rudiments  of  the  cerebrospinal  ganglia  and  differentiate  into  the  afferent  per- 
ipheral neurones,  and  into  some  at  least  of  the  efferent  peripheral  visceral  neu- 
rones (sympathetic)  as  well  as  some  other  accessory  structures  (see  pp.  489 
to  494).  The  peripheral  processes  of  these  ganglion  cells  (afferent  peripheral 
nerve  fibers)  pass  to  the  receptors,  the  central  processes  (afferent  root  fibers)  enter 
the  dorsal  part  of  the  nerve  tube  (Fig.  430).  In  the  case  of  the  special  sense 
organs  there  is  an  interesting  tendency  on  the  part  of  portions  of  the  neural 


452 


TEXT-BOOK  OF  EMBRYOLOGY. 


tube,  either  evaginations  (optic  vesicles,  olfactory  bulbs),  or  ganglia,  to  fuse 
with  ectodermal  thickenings  (placodes)  at  the  site  of  the  future  sense  organs. 
There  appear  to  be  often  two  series  of  ganglionic  placodes  in  the  head,  a 
dorsal  (suprabranchial)  series  and  a  ventral  (epibranchial)  series,  the  latter 
being  often  known  as  gill  cleft  organs.  The  former  appear  to  be  especially 
connected  with  the  development  of  the  acustico-lateral  system,  the  latter  prob- 
ably with  the  gustatory  (see  p.  462).  (Fig.  399).  The  bodies  of  the  efferent 


Neural  crest  cells  - 


Suprabranchial  placode  — 

Mesoderm 

Epibranchial  placode  —  ^Bj^^^^HQBS 

''^'j&vO    6 
Rudiment  of  nerve  —  -piC. 


1-    Notochord 


•3T  Preoralgut 


FIG.  399. — Transverse  section  through  the  head  of  a  7  day  Ammocoetes  in  the  region 
of  the  trigeminal  ganglion,     von  Kupffer. 

neurones  (except  the  sympathetic)  remain  in  the  neural  tube,  lying  in  its 
ventral  half,  and  send  their  axones  out  as  the  efferent  peripheral  nerve  fibers  to 
the  effectors. 

The  formation  of  the  neural  plate  and  its  closure  into  a  tube  are  the  em- 
bryological  expression  of  the  above  noted  tendency  of  highly  specialized  neural 
structures  to  concentrate  and  withdraw  from  the  surface  (p.  448).  The  same 
is  true  of  the  less  highly  specialized  placodes,  in  which  this  process  is  not  carried 
so  far.  The  neural  plate  may  thus  be  regarded  as  the  oldest  placode.  The 
afferent  peripheral  neurones  would  naturally  originate  from  the  borders  of  this 
plate,  such  portions  being  the  last  to  separate  from  the  non-neural  ectoderm 
or  outer  surface.  They  may  be  regarded  as  the  youngest  portions,  phylo- 
genetically,  of  the  plate,  and  there  seems  to  be  some  variation  among  Chordates 
as  to  the  degree  of  inclusion  of  the  afferent  peripheral  neurones  in  the  plate. 

In  the  neural  tube  thus  formed,  there  can  be  distinguished  four  longitudinal 


THE  NERVOUS  SYSTEM. 


453 


plates  or  zones :    A  ventral  median  plate  (floor  plate] ,  a  dorsal  median  plate  (roof 
plate],  where  the  fusion  occurred,  and  two  lateral  plates  (e.g.,  Fig.  442). 

Two  points  are  to  be  noted:  First,  that  the  neural  plate  is  a  bilateral  struc- 
ture and  the  future  development  of  the  tube  will  naturally  take  place  principally 
in  the  side  walls  or  lateral  plates  of  the  formed  tube;  second,  that  the  primary 
connection  between  the  two  side  walls  is  the  ventral  median  plate,  the  dorsal 
median  plate  having  been  produced  by  a  secondary  fusion.  This  being  the 
case,  the  ventral  connection  between  the  two  lateral  plates  will  naturally  be 
more  extensive  and  possibly  more  primitive  than  the  dorsal.  The  ventral  and 
dorsal  median  plates  do  not  usually  develop  nervous  tissue,  but  bands  of  vertical 
elongated  ependyma  cells.  In  places  the  roof  plate  expands  into  thin  mem- 
branes which  are  covered  with  vascular  mesodermal  tissue  forming  chorioid 
plexuses,  such  as  the  chorioid  plexuses  of  the  lateral,  third  and  fourth  ventricles 
(Fig.  408). 


FIG.  400. — Scheme  of  a  median  sagittal  section  through  a  vertebrate  brain  before 

the  closure  of  the  neuropore.     von  Kupffer, 

A.,  Archencephalon;  £>.,  deuterencephalon;  Ms.,  medulla  spinalis  (spinal  cord);  cd.,  notochord; 
en.,  neuronteric  canal;  ek.,  ectoderm;  en.,  entodernv  /.,  infundibulum;  up.,  neuropore;  pv.t 
ventral  cephalic  fold;  tp.,  tuberculum  posterius. 

It  has  already  been  seen  that  even  at  its  first  appearance  the  neural  plate 
exhibits  a  differentiation  into  an  anterior  expanded  part,  the  brain,  and  a 
posterior  narrower  part,  the  spinal  cord.  After  closure,  in  many  Vertebrates  at 
least,  a  three-fold  division  can  be  made  out:  (i)  A  caudal  part  of  the  neural 
tube,  the  spinal  cord,  which  gradually  expands  cranially  into  (2)  the  caudal  part 
of  the  brain  (deuterencephalon,  v.  Kupffer)  (Fig.  400).  These  two  parts  lie 
above  the  notochord  and  all  the  typical  cerebrospinal  nerves  are  connected 
with  them.  (3)  Cranially,  at  the  anterior  end  of  the  notochord,  the  brain  wall 
expands  ventrally  forming  the  third  portion  (archencephalon) .  At  the  forward 
extremity  is  seen  the  anterior  neuropore.  The  deuterencephalon  is  thus  an 
epichordal  part  of  the  brain,  while  the  archencephalon  is  prechordal.  At  the 
boundary  between  the  two  is  a  ventral  infolding  of  the  brain  wall — the  ventral 
cephalic  fold  (plica  encephali  ventralis) .  At  this  stage  the  brain  resembles  that 
of  Amphioxus  in  many  respects.  From  each  side  wrall  of  the  archencephalon 


454  TEXT-BOOK  OF  EMBRYOLOGY. 

an  evagination  appears,  the  optic  vesicle  (Fig.  414)  which  develops  into  the 
retina  and  optic  nerve. 

In  the  next  stage  (Fig.  401),  there  is  a  tendency  for  the  neural  tube  to  bend 
ventrally  around  the  anterior  end  of  the  notochord.  This  bending  is  the 
cephalic  flexure.  At  the  same  time  the  dorsal  wall  above  the  cephalic  fold  be- 
comes expanded  and  is  marked  off  from  that  part  of  the  dorsal  wall  lying 
caudally  by  a  transverse  constriction,  the  rhombo-mesencephalic  fold,  and  from 
the  part  of  the  dorsal  wall  lying  cranially  by  another  transverse  fold  at  the 
site  of  the  future  posterior  commissure.  The  middle  part  of  the  brain,  the 
roof  of  which  is  thus  marked  off,  is  the  mid-brain  or  mesencephalon.  Its 
floor  is  the  middle  projecting  part  of  the  ventral  cephalic  fold.  The  cephalic 
expansion  of  the  brain,  practically  the  former  archencephalon,  is  now  the 


FIG.  401. — Scheme  of  a  median  sagittal  section  through  a  vertebrate  brain  after  the  formation 

of  the  three  primary  brain  expansions,     von  Kupfter, 

P..  prosencephalon;  M.,  mesencephalon;  R.,  rhombencephalon;  Ms.,  spinal  cord;  civ.,  chiasma  emi- 
nence; /.,  infundibulum;  It.,  lamina  terminalis;  pv.,  ventral  cephalic  fold;  pn.,  processus 
neuroporicus;  pr.,  rhombo-mesencephalic  fold;  r.1,  unpaired  olfactory  placode;  ro.,  recessus 
(prae-?)  opticus;  tp.,  tuberculum  posterius. 

fore-brain  or  prosencephalon  and  the  caudal  expansion  is  the  rhombic  brain  or 
rhombencephalon. 

These  three  primary  brain  expansions  ("vesicles"),  the  fore-brain,  mid- 
brain  and  rhombic  brain,  are  constant  throughout  the  Vertebrates.  Beginning 
at  the  location  of  the  former  neuropore  (processus  neuroporicus)  and  passing 
caudally  along  the  floor  of  the  fore-brain  we  have  the  lamina  terminalis  or  end- 
wall  of  the  brain,  containing  a  thickening  which  indicates  the  site  of  the  future 
anterior  (cerebral)  commissure,  next  the  recessus  prceopticus,  then  another  thick- 
ening, the  chiasma  eminence,  and  finally  a  diverticulum,  the  recessus  postopticus 
and  injundibulum  (Fig.  401). 

At  a  later  stage  (Fig.  402),  there  appear  two  evaginations  in  the  roof  of  the 
fore-brain,  the  anterior  epiphysis  or  paraphysis  and  the  posterior  epiphysis  or 
epiphysis  proper  (pineal  body).  Immediately  caudal  to  the  paraphysis  is  a 
transverse  infolding  of  the  brain  roof,  the  velum  transversum.  The  line  aa 


THE  NERVOUS  SYSTEM.  455 

(Fig.  402)  extending  from  this  fold  to  the  optic  recess  indicates  the  location  of  a 
fold  in  the  side  walls  in  some  forms  and  is  taken  by  some  as  the  boundary  be- 
tween two  subdivisions  of  the  fore-brain,  the  end-brain  or  telenccphalon  and  the 
inter-brain  or  diencephalon.  Cranial  to  the  epiphysis  proper,  is  a  commissure 
in  the  dorsal  wall  (commissura  habemdaris^  connecting  two  structures  which 
develop  in  the  crests  of  the  side  walls,  the  ganglia  habenula. 

From  the  dorsal  part  of  the  telencephalon  is  developed  the  pallium.  The 
ventral  anterior  part  evaginates  toward  the  olfactory  pit,  its  end  receiving  the 
olfactory  fibers.  This  region  is  often  termed  the  rhinencefhalon.  Thickenings 
of  the  basal  lateral  walls  of  the  telencephalon  form  \h^cozpora  striata. 


FIG.  402. — Scheme  of  a  median  sagittal  section  through  a  vertebrate  brain  showing 

the  five-fold  division  of  the  brain,     von  Kupfler. 

T.,  Telencephalon;  D.:  diencephalon;  M.,  mesencephalon;  Mt.,  metencephalon;  Ml.,  myelence- 
phalon;  c.y cerebellum;  cc.,  cerebellar  commissure;  ch.,  habenular  commissure;  cp.,  posterior 
commissure;  cw.,  chiasma  eminence;  e.,  epiphysis;  e1.,  paraphysis;  J.,  infundibulum;  //., 
lamina  terminalis;  />«.,  processusneuroporicus;  pr.,  rhombo-mesencephalicfold;  pv.,  ventral 
cephalic  fold;  ro.}  recessus  (prae-)  opticus;  si.,  sulcus  intraencephalicus  posterior;  tp.,  tuber- 
culum  posterius.  The  lines  aa.,  dd  and  ft  indicate  the  boundaries  between  four  divisions. 

The  roof  of  the  mesencephalon  finally  develops  the  "optic  lobes"  The 
thickened  part  of  the  roof  lying  immediately  caudal  to  the  rhombo-mesen- 
cephalic  fold  develops  into  the  cerebellum.  The  part  of  the  tube  of  which  this 
forms  the  roof  is  often  called  the  hind-brain  or  metencephalon,  while  the  rest  of  the 
rhombencephalon  is  then  termed  the  after-brain  or  myelencephalon.  The  roof  of 
this  portion,  which  has  become  very  thin  in  the  course  of  its  development,  forms 
the  epithelial  part  of  the  tela  chorioidea  of  the  fourth  ventricle.  The  con- 
stricted portion  of  the  tube  between  the  rhombic  brain  and  mid-brain  is  the 
isthmus. 

The  above  subdivisions  of  the  three  primary  expansions  into  five  parts 
(end-,  inter-,  mid-,  hind-  and  after-brains),  especially  the  subdivisions  of  the 
rhombic  brain,  do  not  have  the  morphological  value  of  the  three  primary 


456 


TEXT-BOOK  OF  EMBRYOLOGY. 


divisions  but  have  a  certain  value  for  descriptive  purposes.  The  cavities  of 
the  brain  are  the  ventricles  and  their  connecting  passages,  namely,  the  third 
ventricle  of  the  diencephalon  and  the  fourth  ventricle  of  the  rhombencephalon, 
the  two  being  connected  by  the  mid-brain  cavity  (aquceductus  Sylvii) .  The 
telencephalon  usually  develops  a  more  or  less  paired  character,  its  cavities 
being  then  paired  diverticula  of  the  unpaired  fore-brain  cavity  and  known  as 
the  lateral  ventricles. 

Before  the  closure  of  the  brain  part  of  the  neural  tube,  transverse  constric- 
tions appear  across  the  neural  plate.     The  transverse  rings  into  which  the 


FIG.  403. — Chick  embryos;  i,  of  22  hours'  incubation;  2,  of  24  hours;  3,  of  25^  hours;  4,  of  26 

hours,  showing  respectively  2,  5,  6,  and  7  primitive  segments.     Hill. 

cp.,  Caudal  limit  of  fore-brain;  />-.,  caudal  limit  of  mid -brain;  «.,  first  primitive  segment; 
ps.}  primitive  streak;  i-n,  neuromeres. 


tube,  when  completed,  is  thus  divided  are  known  as  neuromeres.  They  are 
held  to  represent  a  primitive  segmentation  of  the  head,  similar,  perhaps,  to 
that  exhibited  by  the  spinal  nerves  and  segmental  somatic  musculature  (primi- 
tive segments)  of  the  trunk.  The  neuromeres  may  appear  before  the  head 
somites.  To  what  extent  they  correspond  to  the  somites  or  to  the  visceral 
segmentation  (p.  460)  and  also  to  the  cranial  nerves  is  a  matter  of  dispute. 
Concerning  their  number  there  have  been  various  views,  the  evidence  inclining 
to  three  in  the  fore-brain,  two  in  the  mid-brain  and  six  in  the  rhombic  brain 
(Fig.  403).  Their  presence  and  number  are  most  in  doubt  in  the  cephalic  end 
of  the  tube,  the  highly  modified  prosencephalon. 


THE  NERVOUS  SYSTEM.  457 

The  general  features  of  the  vertebrate  nervous  system  which  especially 
illuminate  conditions  met  with  in  the  human  nervous  system  are  the  following: 
(i)  The  correlation  between  the  peripheral  structures  (receptors  and  effectors) 
and  the  nervous  system.  (2)  The  distinction  between  the  epichordal  and  pre- 
chordal  portions  of  the  brain.  The  latter  (fore-brain)  is,  in  accordance  with  its 
anterior  position  (comp.  p.  450),  the  most  highly  modified  part  of  the  neural 
tube.  (3)  The  distinction  between  the  segmented  and  suprasegmental  parts 
of  the  brain  (Adolf  Meyer).*  The  segmental  part  of  the  brain  is  that  portion 
in  more  immediate  connection  with  peripheral  segmental  structures.  Its  epi- 
chordal part  is  spinal-like  and  most  clearly  segmental.  Its  prechordal  part, 
both  as  to  its  peripheral  and  central  portions,  is  so  highly  modified  that  its 
segmental  character  is  more  obscure.  It  and  the  rest  of  the  prechordal  brain 
are  most  conveniently  treated  together  as  fore-brain.  The  suprasegmental 
parts  of  the  brain,  or  higher  coordinating  centers,  are  the  cerebellum,  mid- 
brain  roof  and  the  pallium  (cerebral  hemispheres).  Their  general  functional 
significance  has  been  mentioned  (p.  450).  Some  of  their  general  structural 
characteristics  are :  First,  that  they  are  each  expansions  of  the  dorso-lateral 
walls  of  the  neural  tube;  second,  that  in  them  the  neurone  bodies  are  placed 
externally  and  in  layers  (cortex),  the  nerve  fibers  (white  matter)  lying  within; 
third,  that  each  appears  to  have  originally  had  an  especially  close  relation  with 
some  one  of  the  three  great  sense  organs  of  the  head,  the  olfactory,  \isual  or 
acustico-lateral  system;  fourth,  that  each  is  connected  with  the  rest  of  the  brain 
by  bundles  of  centripetal  and  centrifugal  fibers,  and  often  there  are  specialized 
groups  of  neurone  bodies  in  other  parts  of  the  brain  for  the  origin  or  recep- 
tion of  such  bundles.  Each  higher  center  has  also  its  own  system  of  association 
neurones. 

It  will  accordingly  be  most  convenient  to  consider:  (i)  the  spinal  cord,  (2) 
the  segmental  part  of  the  epichordal  brain,  (3)  the  cerebellum,  (4)  the  mid- 
brain  roof,  (5)  the  prosencephalon. 

Spinal  Cord  and  Nerves. 

As  already  brought  out,  there  are  two  principal  morphological  differences 
between  the  afferent  and  efferent  peripheral  neurones.  First,  the  neurone 
bodies  of  the  former  are  located  outside  the  neural  tube,  w^hile  the  neurone 
bodies  of  the  latter  lie  within  the  walls  of  the  neural  tube.  Second,  the  afferent 

*  This  distinction  apparently  ignores  the  fact  that  the  primitive  neuromeric  segmentation  of  the 
neural  tube  involves  its  dorsal  as  well  as  its  ventral  walls  and  thus  "suprasegmental"  as  well  as  "seg- 
mental "  structures  were  originally  segmental.  This  may  be  granted,  but  while  the  demonstration 
of  the  primitive  segmentation  of  the  neural  tube  may  be  valuable  as  showing  the  primitive  mechan- 
ism which  has  undergone  later  modifications,  the  importance  of  such  later  modifications  renders  the 
above  distinction  necessary.  The  main  significance  of  the  nervous  system  is  its  associative  character 
and  its  progressive  development  is  not  as  a  segmental,  but  as  a  more  and  more  highly  developed 
associating  mechanism. 


458  TEXT-BOOK  OF  EMBRYOLOGY. 

nerves  enter  the  dorsal  part  of  the  lateral  walls  of  the  tube,  while  the  efferent 
nerves  leave  the  ventral  part  of  the  lateral  walls,  their  neurone  bodies  lying  in 
this  ventral  part.  The  effect  of  this  upon  the  structural  arrangements  within 
the  tube  is  the  production  in  the  tube  of  two  columns  of  neurone  bodies,  a  dorsal 
gray  column  for  the  reception  of  the  dorsal  or  afferent  roots  and  a  ventral 
gray  column  containing  the  efferent  neurone  bodies. 

Another  important  differentiation  arises  apparently  from  the  important 
physiological  difference  in  general  character  between  the  activities  of  what  may 


FIG.  404. — Transverse  section  through  the  body  of  a  typical  Vertebrate,  showing  the  peripheral 

(segmental)  nervous  apparatus.     Froriep. 
Small  dots,  afferent    visceral    neurones;    coarse  dots,  afferent    somatic   neurones;    dashes,  efferent 

visceral  (ventral  root  and  sympathetic)  neurones;  lines,  efferent  somatic  neurones. 
Darm,  gut;    Ggl.  spin.,  spinal  ganglion;    Ggl.  vert.,  vertebral  sympathetic  ganglion;    Ggl.  mesent., 

mesenteric  sympathetic  ganglion.    The  peripheral  sympathetic  ganglionic  plexuses  (Auer- 

bach   and  Meissner)  are  not  shown.     Muse.,  muscle;    Rad.  dors.,  dorsal  root;    Rad.  vent., 

ventral  root;  R.  comm.,  white  ramus  communicans. 
Two  sympathetic  neurones  are  represented  as  intercalated  in  the  visceral  efferent  pathway.     It  is 

doubtful  if  there  should  be  more  than  one. 

be  termed  the  internal  (visceral  or  splanchnic}  and  the  external  (somatic)  struc- 
tures. Internal  activities  are  to  a  certain  extent  independent  of  activities 
which  have  to  do  more  with  the  reactions  of  the  organism  to  the  external  world, 
and  consequently  their  nervous  mechanisms  have  a  more  or  less  independent 
character,  forming  what  is  often  called  the  autonomic  (sympathetic)  system. 
This  independence  is  exhibited  structurally  by  the  intercalation  in  the  per- 
ipheral pathway  of  additional  neurones,  whose  bodies  form  visceral  ganglia 


THE  NERVOUS  SYSTEM.  459 

connected  in  various  ways  among  themselves  and  probably  having  their  own 
reflex  arcs  or  plexuses.  These  ganglia  are  nevertheless  to  some  extent  under 
the  control  of  the  efferent  neurones  of  the  central  nervous  system,  some  of 
which  send  their  axones  to  such  ganglia  (Fig.  404).  There  are  thus  in  the 
central  nervous  system  two  categories  of  efferent  peripheral  neurones,  those 
innervating  visceral  structures  "via  sympathetic  ganglia  and  those  innervating 
somatic  structures.  The  bodies  of  the  somatic  efferent  neurones  are  located 
in  the  ventral  gray  matter  of  the  nerve  tube,  while  the  bodies  of  the  splanchnic 
efferent  neurones  are  believed  to  occupy  more  central  and  lateral  positions  in 
the  lower  half  of  the  gray  matter  of  the  neural  tube  (Fig.  404).  It  is  uncer- 
tain whether  there  are  similar  afferent  splanchnic  neurones  in  the  sympathetic 
ganglia,  and  thus  distinct  from  those  in  the  spinal  ganglia,  or  whether  these  all 
lie  in  the  spinal  ganglia  and  are  consequently  not  fully  differentiated  from  the 
somatic  afferent  neurones. 

The  muscular  segmentation  of  the  trunk  has  already  been  mentioned  and 
also  the  corresponding  segmental  arrangement  of  the  spinal  nerves.  Local 
extensions  of  this  musculature  and  of  its  overlying  cutaneous  surface  in  the 
form  of  fins  and  limbs  cause  corresponding  increase  in  the  size  of  those  seg- 
ments of  the  cord  innervating  them.  This  is  due  to  the  increased  number  of 
afferent  fibers  and  consequent  increase  in  the  dorsal  white  columns  and  in  the 
receptive  dorsal  gray  columns,  also  to  the  increase  in  the  number  of  efferent 
peripheral  neurones  whose  bodies  occupy  the  ventral  gray  column  (e.g.,  cervi- 
cal and  lumbar  enlargements).  (Compare  also  the  differentiation  in  the 
cervical  cord  and-  lower  medulla  of  the  columns  and  nuclei  of  Goll  for  the 
lower  extremities  and  those  of  Burdach  for  the  upper  extremities). 

In  general,  the  intermediate  neurones  of  the  cord  fall  into  two  categories; 
intersegment al  (ground  bundles),  connecting  cord  segments,  and  those  send- 
ing long  ascending  bundles  to  suprasegmental  structures  (see  pp.  472  and  473.) 

The  Epichordal  Segmental  Brain  and  Nerves. 

The  principal  peripheral  structures  which  exert  a  determining  influence  on 
the  structure  of  the  epichordal  brain  are :  The  mouthy  the  respiratory  apparatus 
(gills  and  later  lungs),  and  two  specialized  sensory  somatic  structures,  the 
acustico-lateral  system  and  the  optic  apparatus. 

In  the  gills  we  have  essentially  a  series  of  vertical  clefts  forming  communica- 
tions between  the  pharynx  and  the  exterior,  the  intervals  between  the  clefts 
being  the  gill  arches.  The  musculature  of  the  gill  arches  is  morphologically 
splanchnic  (pp.  302  and  311).  The  gill  or  branchial  musculature  is  in  closer 
relations  with  stimuli  from  the  external  world  than  is  the  visceral  musculature 
of  the  body.  As  a  result  of  this  the  former  is  not  of  the  smooth  involuntary 


460  TEXT-BOOK  OF  EMBRYOLOGY. 

type,  like  the  visceral  musculature  of  the  body,  but  is  of  the  striated  voluntary 
type,  like  the  somatic  musculature.  The  branchial  receptors  are  naturally 
visceral  in  character  and  there  is  also  in  this  region  a  series  of  specialized 
visceral  receptors,  the  end  buds  of  the  gustatory  system.  The  development  of 
this  whole  specialized  visceral  apparatus  in  this  region  of  the  head  has  appar- 
ently caused  a  corresponding  reduction  of  the  somatic  musculature. 

The  musculature  of  the  mouth  is  also  splanchnic,  the  mouth  itself  being- 
regarded  by  many  morphologists  as  a  modified  pair  of  gill  clefts  which  has  re- 
placed an  older  mouth  lying  further  forward  in  the  region  of  the  hypophysis. 
The  existence  of  this  series  of  gill  clefts  has  naturally  caused  a  branchiomeric 
or  splanchnic  segmentation  of  the  musculature  of  this  region  as  opposed  to  the 
somatic  muscular  segmentation  seen  in  the  trunk.  Whether  these  two  kinds 
of  segmentation  correspond  in  this  region  is  uncertain.  (In  this  connection  see 
Fig.  428  and  p.  496.) 

In  the  acustico-lateral  system  three  parts  may  be  distinguished :  (i)  a  remark- 
able series  of  cutaneous  sense  organs,  extending  in  lines  over  the  head  and  body 
and  known  as  the  lateral  line  organs;  (2)  the  vestibule,  including  the  semicircu- 
lar canals;  (3)  the  cochlea  (organ  of  hearing  proper — Cord's  organ) .  In  the 
higher  Vertebrates,  the  lateral  line  organs  have  disappeared,  owing  to  a  change 
from  a  water  to  a  land  habitat;  the  labyrinth  has  remained  unchanged,  and 
the  cochlea  has  undergone  a  much  higher  development  and  specialization. 

Regarding  the  optic  apparatus,  it  is  sufficient  to  point  out  here  that  its  motor 
part,  the  eye  muscles,  is  usually  taken  to  represent  the  sole  remaining  somatic 
musculature  belonging  to  the  head  proper. 

The  peripheral  nerves  of  the  epichordal  part  of  the  brain  have  fundamen- 
tally the  same  arrangements  as  the  spinal  nerves,  namely,  the  peripheral  af- 
ferent neurone  bodies  are  separate  from  the  nerve  tube,  forming  ganglia,  while 
the  bodies  of  the  efferent  neurones  are  located  centrally  in  the  morphologically 
ventral  portions  of  the  lateral  walls  of  the  nerve  tube.  There  are,  however, 
important  differences,  clearly  correlated  with  the  peripheral  differentiations  and 
specializations  outlined  above,  and  affecting  the  afferent  and  efferent  nerves. 

First  to  be  considered  is  the  afferent  part  of  the  trigeminus  (Figs.  405  and 
406).  The  peripheral  branches  of  the  ganglion  (semilunar  or  Gasserian 
ganglion)  of  this  nerve  innervate  that  part  of  the  external  (somatic)  surfaces  of 
the  head  (skin  and  stomodaeal  epithelium)  which  have  not  been  encroached 
upon  by  the  spinal  afferent  nerves.  This  nerve  is  accordingly  more  strictly 
comparable  with  the  afferent  spinal  nerves.  The  central  processes  of  the 
semilunar  ganglion  cells,  after  entering  the  brain,  form  a  separate  descending 
bundle,  the  spinal  V.  It  is  interesting  to  note  that  the  terminal  nucleus  of 
this  bundle  of  fibers  is  the  morphological  continuation  in  the  brain  of  the 
dorsal  gray  column  of  the  cord.  The  extensiveness  of  the  area  innervated  by 


THE  NERVOUS  SYSTEM. 


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3 

" 


462  TEXT-BOOK  OF  EMBRYOLOGY. 

the  trigeminus  may  be  partly  due  to  disappearance  or  specialization  of  anterior 
somatic  nerves  and  also  to  the  growth  of  the  head. 

The  organs  of  the  lateral  line  are  innervated  by  a  quite  distinct  system  of 
ganglionated  afferent  nerves  whose  central  connections  are  nearly  identical  with 
those  of  the  acoustic  (Fig.  405).  With  the  disappearance  of  the  lateral  line 
organs  and  the  specialization  of  the  cochlear  part  of  the  ear  vesicle,  there  is  a 
disappearance  of  the  lateral  line  nerves  (comp.  Figs.  405  and  406)  and  a  well- 
marked  division  of  the  acoustic  nerve  into  vestibular  and  cochlear  portions, 
the  former  innervating  the  older  vestibulo-semicircular  canal  portion,  the  latter, 
the  more  recent  cochlea.  Centrally,  the  vestibular  nerve  forms  also  a  descend- 
ing bundle  of  fibers  and  has  its  own  more  or  less  specialized  terminal  nuclei. 
The  latter  is  also  true  of  the  cochlear  nerve. 

The  afferent  portions  of  the  facial,  glossopharyngeal  and  vagus  nerves  in- 
nervate the  splanchnic  receptors  of  the  pharyngeal  and  branchial  surfaces  as 
well  as  of  a  large  part  of  the  viscera.  The  facial,  glossopharyngeal  and  vagus 
also  innervate  the  specialized  splanchnic  receptors,  the  gustatory  system  men- 
tioned above.  This  system  of  taste  buds  has  a  very  extensive  development  in 
certain  lower  Vertebrates,  especially  the  Bony  Fishes.  In  the  latter  the 
system  of  nerves  innervating  these  structures  is  naturally  much  more  extensive 
and  its  central  terminations  and  nuclei  cause  important  modifications  of  the 
medulla.  In  Mammals  the  remnants  of  this  system  are  represented  by  the 
taste  buds  in  the  mouth,  the  nerves  innervating  them  being  the  chorda  tympani 
branch  of  the  facial  and  the  lingual  branch  of  the  glossopharyngeal  (Fig.  406). 
The  central  branches  of  the  ganglia  of  these  three  nerves,  after  entering  the 
brain,  form  a  descending  bundle  of  fibers,  ihejractus  solitarius  (or  communis). 

The  somatic  musculature  of  the  head,  as  above  mentioned,  is  usually  taken 
to  be  represented  by  the  eye  muscles  and,  later,  the  tongue  muscles.  The 
tongue  is  one  of  the  newer  structures,  rising  in  importance  with  the  change  to 
a  land  habitat,  and  its  muscles  are  probably  an  invasion  from  the  neck  region 
caudal  to  the  branchial  arches  (p.  321).  The  eye  muscles  are  innervated  by 
the  III,  IV  and  VI  cranial  nerves,  the  tongue  muscles  by  the  XII  which  is  a 
more  recent  addition  to  the  cranial  nerves.  All  of  these  nerves  are  charac- 
terized by  having  their  neurone  bodies  located  in  the  most  medial  (morpholog- 
ically most  ventral)  portions  of  the  lateral  brain  walls,  and  they  all,  except  the 
IV,  emerge  near  the  mid-ventral  line.  In  these  respects  they  resemble  the 
major  or  somatic  part  of  the  ventral  spinal  roots.  (For  illustration  see  Figs. 
427,  405  and  406). 

The  splanchnic  musculature  of  the  jaws  and  the  branchial  arches  is  inner- 
vated by  the  efferent  portions  of  the  V,  VII,  IX,  X  (and  XI).  The  neurone 
bodies  or  nuclei  of  origin  of  these  nerves  lie  more  laterally  than  those  of  the  III, 
IV,  VI  and  XII,  and  their  axones  also  leave  the  nerve  tube  more  laterally 


THE  NERVOUS  SYSTEM. 


463 


464  TEXT-BOOK  OF  EMBRYOLOGY. 

along  with  the  incoming  afferent  fibres.  These  nerves  all  exhibit  a  character- 
istic segmental  arrangement  corresponding  to  that  of  the  gill  clefts.  The 
VII,  IX,  and  the  various  nerves  making  up  the  X,  divide  dorsal  to  the  cor- 
responding gill  clefts  into  prebranchial  and  postbranchial  branches,  also 
giving  off  suprabranchial  branches.  The  efferent  element,  or  component, 
forms  a  part  of  each  postbranchial  branch.  These  relations  are  shown  clearly 
in  the  accompanying  diagrams  (Figs.  405  and  406).  Part  of  the  vagus  also 
innervates  the  viscera  and  this  nerve  is  thus  divisible  into  branchial  and  visceral 
portions. 

Two  peculiarities  may  be  noted  in  regard  to  these  splanchnic  nerves :  First, 
that  the  afferent  portions  have  ganglia  resembling  those  of  the  spinal  nerves; 
second,  that  the  branchial  efferent  portions  consist  simply  of  one  neurone 
proceeding  all  the  way  from  the  nerve  tube  to  the  muscle  innervated,  thus 
resembling  the  somatic  rather  than  the  visceral  nerves  of  the  trunk.  As  al- 
ready noted  (p.  459),  these  nerves  regulate  activities  somatic  in  character  but 
involving  splanchnic  structures.  It  is  thus  seen  that  the  dominating  factor  is 
functional  rather  than  morphological — present  functional  necessities  modify 
those  of  the  past. 

With  the  change  from  a  water  to  a  land  habitat  and  the  accompanying 
disappearance  of  gills  and  appearance  of  lungs,  we  have  various  suppressions 
and  modifications  of  the  branchial  musculature  (Fig.  406).  There  are  two 
striking  specializations  of  the  branchial  musculature.  One  is  the  origin  of 
the  facial  (mimetic)  musculature  in  the  highest  Vertebrates.  This  is  derived 
from  the  muscles  of  the  hyoid  arch,  innervated  naturally  by  extensions  of  the 
facial  nerve.  The  other  is  a  specialization  of  muscles,  probably  of  the  caudal 
branchial  arches,  into  cervico-cranial  muscles  (head-movement),  innervated  by 
what  may  be  considered  a  caudal  extension  of  the  vagus  nerve,  namely,  the 
spinal  accessory  (p.  496).  The  splanchnic  laryngeal  musculature  and  its 
nerves  show  a  certain  degree  of  specialization  (sound-production)  in  higher 
forms.  The  efferent  V  is  naturally  a  large  constant  nerve,  in  correlation  with 
the  uniformly  developed  jaw  musculature  in  all  jaw-bearing  (gnathostome) 
Vertebrates  (Figs.  405  and  406).  These  various  changes  in  peripheral 
structures  are  thus  due  either  to  environmental  influences  or  to  developments 
within  the  central  nervous  system  (p.  450).  One  of  the  most  important  en- 
vironmental influences  is  the  change  from  a  water  to  a  land  habitat.  The 
influence  of  the  central  nervous  system  is  shown  in  the  further  development 
and  specialization  of  a  number  of  peripheral  structures  as  motor  "instru- 
ments" of  suprasegmental  mechanisms. 

The  effects,  then,  of  the  peripheral  arrangements  upon  the  arrangements 
within  the  neural  tube  are:  (i)  The  formation  of  separate  tracts  and  terminal 
nuclei  for  (a)  the  unspecialized  somatic  afferent  V  nerve  (spinal  V  and  posterior 


THE  NERVOUS  SYSTEM. 


465 


horn) ;  (b)  the  specialized  somatic  vestibular  nerve  (descending  or  spinal  VIII 
and  various  terminal  nuclei)  and  also  the  cochlear  nerve  and  its  various  termi- 
nal nuclei;  (c)  the  splanchnic  afferent  nerves  (tractus  solitarius  and  its 
terminal  nuclei).  (2)  The  separation  of  the  efferent  neurone  bodies  lying  in  the 
neural  tube  into  two  main  longitudinal  series  of  nuclei  (a)  the  somatic  efferent 
nuclei,  occupying  a  more  medial  position,  their  axones  emerging  from  the  neural 
tube  as  medial  ventral  nerve  roots;  (b)  the  splanchnic  efferent  nuclei  occupying 
a  more  lateral  position,  their  axones  emerging  laterally  and  forming  mixed 
roots  with  the  incoming  afferent  fibers  (Fig.  407). 


FIG.  407. — Diagram  of  a  transverse  section  through  the  lower  human  medulla  showing  the  origin  of 
the  X  and  XII  cranial  nerves.     Schdfer. 

gy  Ganglion  cell  of  afferent  vagus  sending  central  arm  (root  fiber)  to  solitary  tract  (f.s.}  and  col- 
lateral to  the  nucleus  of  the  solitary  tract  (/.  s.  n.).  It  is  not  certain  that  the  axones  of  the 
cells  of  this  terminal  nucleus  take  the  course  indicated  in  the  figure,  n.amb.,  nucleus  am- 
biguus  and  d.  n.  X,  dorsal  efferent  nucleus  of  the  vagus,  both  of  which  send  out  axones  as  the 
efferent  root  fibers  of  the  vagus.  These  two  represent  the  lateral  or  splanchnic  efferent  nuclei 
of  this  region,  n.  XII,  nucleus  of  the  hypoglossus  the  axones  of  which  pass  out  medially  as 
efferent  root  fibers  of  the  XII.  This  nucleus  represents  the  medial  or  somatic  efferent  nuclei 
of  this  region,  f.s..  tractus  solitarius  or  descending  roots  of  vagus,  glossopharyngeus  and 
facial;  d.  V.,  descending  spinal  root  of  the  trigeminus;  r.,  restiform  body;  o.,  inferior  olivary 
nucleus  (''olive");  pyr~  pyramid. 

The  intermediate  neurones  of  the  epichordal  segmental  brain,  as  well  as 
of  the  cord,  fall  into  two  general  systems.  One  of  these  is  the  system  of 
inter  segmental  neurones,  connecting  various  segments  of  the  segmental  brain 
and  cord.  This  system  may  be  collectively  termed  the  ground  bundles  (of  the 
cord)  and  reticular  formation  (of  the  brain) .  These  neurones  may  be  regarded 
as  not  only  furnishing  the  various  reflex  communications  between  the  afferent 
and  efferent  cerebrospinal  peripheral  neurones,  but  as  also  forming  a  system 
upon  which  the  descending  neurones  from  the  higher  coordinating  centers 
(suprasegmental  structures)  act,  before  the  efferent  peripheral  neurones  are 
reached.  This  system  may  thus  be  regarded  in  general  as  more  closely  associ- 


466  TEXT-BOOK  OF  EMBRYOLOGY. 

ated  with  the  efferent  than  with  the  afferent  peripheral  neurones.  Certain 
tracts  in  this  system  and  their  nuclei  of  origin  have  reached  a  considerable 
degree  of  differentiation,  due  principally  to  association  with  higher  centers. 
Among  these  differentiated  reticulo-spinal  tracts  may  be  mentioned  the  medial 
longitudinal  fasciculus,  the  rubro-spinal  tract,  and  the  various  tracts  from 
Deiters'  nucleus.  The  other  system  consists  of  nuclei  which  are  associated 
with  the  afferent  axones  as  their  terminal  nuclei,  the  axones  of  which  form  long 
afferent  tracts  to  suprasegmental  structures.  Especially  well-marked  differ- 
entiations of  nuclei  and  tracts  of  this  system  are  usually  due  both  to  its  con- 
nections with  peripheral  structures  and  with  the  higher  centers.  The  principal 
afferent  suprasegmental  tracts  to  the  cerebellum  are  mentioned  below  (p.  466). 
Those  to  mid-brain  roof  and  (via  added  neurones)  to  pallium  are  the  medial 
fillet  or  lemniscus  from  the  nuclei  of  the  columns  of  Goll  and  Burdach,  the 
lateral  lemniscus  from  the  cochlear  terminal  nuclei  and  other  ascending  tracts 
from  terminal  nuclei  of  peripheral  afferent  neurones. 

The  Cerebellum. 

The  other  great  factor  (see  p.  450)  affecting  the  structure  of  the  epichordal 
brain  is  the  development  in  it  of  two  higher  coordinating  centers  or  supraseg- 
mental structures,  the  cerebellum  and  optic  lobes.  The  cerebellum  is  a  develop- 
ment of  the  dorsal  part  of  the  lateral  walls  of  the  tube  just  caudal  to  the  isthmus 
and  was  probably  primarily  developed  in  correlation  with  the  acustico-lateral 
system,  especially  with  the  lateral  line  and  vestibule-semicircular  canal 
portions  (p.  460).  Due  probably  to  the  fact  that  it  is  thus  an  important 
"equilibrating"  mechanism,  the  cerebellum  has  acquired  other  important  con- 
nections besides  its  original  ones  with  the  acustico-lateral  system.  In  the 
vertebrate  series  it  is  especially  developed  in  all  active  balancing  forms  (Fig.  408) . 
In  Mammals  it  has  acquired  important  connections  with  the  greatly  enlarged 
pallium  (cerebral  hemispheres),  in  accordance  with  its  general  regulative  in- 
fluence (static  and  tonic)  upon  motor  reactions.  The  great  development  of  the 
cerebellum  has  profoundly  modified  the  anatomical  arrangements  of  the  rest  of 
the  brain  and  cord,  owing  to  its  numerous  and  massive  connections.  The  fol- 
lowing important  masses  of  gray  matter  and  fiber  bundles  may  be  mentioned  as 
cerebellar^a^em^_connections :  Clarke's  column  cells,  and  other  cells  in  the 
cord,  and  the  spino-cerebellar  tracts;  the  lateral  nuclei,  inferior  olives  and  the 
restiform  body  in  the  medulla;  part  of  the  pes  pedunculi,  the  pontile  nuclei  and 
middle  peduncle  of  the  cerebellum.  The  superior  cerebellar  peduncle  to  the 
red  nucleus,  together  with  tracts  to  Deiter's  nucleus,  belong  to  the  cerebellar 
efferent  connections.  The  cortico-pontile  portion  of  the  pes,  the  pontile  nuclei 
and  the  middle  peduncle  represent  the  most  recently  developed  cerebral  con- 
nections (comp.  pp.  470-472  and  Fig.  409). 


THE  NERVOUS  SYSTEM.  467 

The  Mid-brain  Roof. 

This  expansion  of  the  dorsal  part  of  the  neural  tube  constitutes  a  higher 
coordinating  center  for  impulses  received  by  various  somatic  nerves — spinal, 
cochlear  and  optic.  Owing  to  its  being,  in  all  forms  below  Mammals,  the 
principal  visual  center,  the  optic  part  (optic  lobes)  varies  in  proportion  to  the 
development  of  the  eye,  animals  with  poorly  developed  eyes  having  small  optic 
lobes.  In  Mammals,  the  ^>ptic  part  (anterior  corpora  quadrigemina  or  col- 
liculi)  is  relatively  less  important,  owing  to  a  taking  over  of  a  portion  of  its 
coordinating  functions  by  the  neopallium  (pp.  470,  472),  but  the  cochlear  part 
(posterior  corpora  quadrigemina  or  colliculi)  has  increased  in  importance, 
owing  to  the  rise  of  the  cochlear  organ  (organ  of  Corti).  The  centripetal  and 
centrifugal  connections  of  the  mid-brain  roof  are  not  so  massive  or  extensive 
and  consequently  do  not  modify  the  other  parts  of  the  brain  and  cord  as  pro- 
foundly  as  do  those  of  the  cerebellum.  It  sends  descending  tracts  to  after- 
brain  and  cord  segments. 

The  Prosencephalon. 

The  division  of  this  part  of  the  brain  into  the  telencephalon  and  diencephalon 
has  already  been  indicated  (p.  455).  In  the  diencephalon  may  be  noted  (i)  the 
absence  of  the  notochord  ventral  to  the  brain,  thereby  permitting  a  ventral  ex- 
pansion of  the  brain  walls,  the  Jvy^p^wlamuSy  associated  with  an  organ  not 
well  understood,  the  hypophysis;  (2)  certain  more  or  less  vestigial  structures, 
such  as  the  pineal  eyes  (epiphyses),  and  other  primitive  structures,  such  as 
the  ganglia  habenulae,  in  the  dorsal  part,  this  dorsal  portion  being  collectively 
termed  the  epithalamus;  (3)  nuclei  in  (i)  and  (2)  connected  with  olfactory 
and  gustatory  tracts;  (4)  receptive  nuclei  for  the  optic  tract  and  the  cochlear 
path  from  the  posterior  colliculus;  (5)  receptive  nuclei  for  secondary  tracts  from 
the  end  stations  of  more  caudal  somatic  ganglia  (nuclei  of  Goll  and  Burdach 
and  medial  lemniscus).  The  last  two  (4  and  5)  constitute  the  ihalamus  and 
increase  in  importance  in  the  higher  Vertebrates  (see  p.  470,  Fig.  409). 

In  the  telencephalon  there  may  be  roughly  distinguished  an  anterior  and  basal 
part,  the  rhinencephalon,  in  especially  intimate  relations  with  the  olfactory  nerve; 
a  thickening  of  the  basal  wall,  the  corpus  striatum^smd  a  thinner- willed  dorsal 
part,  the  pallium.  The  latter  may  be  regarded  in  a  sense  as  a  dorsal  develop- 
ment of  the  corpus  striatum  and  first  appears  as  a  distinct  structure  in  the 
Amphibia. 

The  peripheral  or  segmental  apparatus  which  are  connected  with  the  pros- 
encephalon  are  the  highly  modified  optic  and  olfactory  organs.  While  the  optic 
apparatus  primarily  originates  from  the  prechordal  brain,  in  the  lower  Verte- 
brates its  highest  coordinating  center,  as  mentioned  above,  lies  partly  in  the 


468  TEXT-BOOK  OF  EMBRYOLOGY. 

epichordal  portion  (optic  lobes).  It  is  possible  that  this  connection  is  secon- 
dary and  contingent  upon  two  functional  necessities,  the  importance  of  cor- 
relation with  stimuli  coming  via  more  caudal  nerves  (cochlear  and  spinal 
nerves),  and  the  innervation  of  its  motor  apparatus  by  epichordal  nerves,  the 
III,  IV  and  VI.  With  the  development  of  the  neopallium  in  Mammals  (see  p. 
477)  and  the  consequent  projection  of  visual  stimuli  upon  it,  the  lower  pre- 
chordal  (thalamic)  centers  form  part  of  the  newer  pathway  to  the  neopallium 
and  thus  increase  in  importance,  while  the  optic  lobes  recede,  assuming  the 
position  of  a  reflex  center,  especially  for  the  visual  motor  apparatus. 

The  olfactory  nerves  enter  the  anterior  extremity  of  the  brain  and  are  con- 
nected by  secondary  and  tertiary  tracts  with  regions  lying  more  caudally,  where 
in  some  cases  the  olfactory  stimuli  are  associated  with  gustatory  and  probably 
with  visual  stimuli.  One  of  these  regions  is  the  hypothalamus  which  receives 
both  olfactory  and  gustatory  tracts  (Herrick) .  More  dorsal  olfactory  pathways 
pass  to  the  epithalamus.  Both  epithalamus  and  hypothalamus  give  rise  to  de- 
scending systems  which  doubtless  ultimately  reach  efferent  nuclei.  In  fact,  this 
part  of  the  brain  presents,  apparently,  a  complicated  primitive  mechanism  for 
the  correlation  especially  of  olfactory  and  gustatory  stimuli,  also  to  some  extent 
of  visual  Stimuli  and  stimuli  via  the  trigeminal  nerve,  the  whole  forming  a  sort 
of  oral  sense,  probably  controlling  the  feeding  activities  (Edinger). 

The  next  factor  in  the  further  development  of  this  part  of  the  brain  is  the 
rise  in  importance  of  the  pallium  upon  which  at  first  are  projected  mainly 
olfactory  stimuli  (Fig.  408). 

A  further  and  still  more  extensive  development  of  the  pallium  arises  when 
other  kinds  of  stimuli  are  projected  to  a  considerable  extent  upon  it,  thus  giving 
rise  to  a  distinction  between  the  older  olfactory  pallium  (archipallium)  and  the 
newer  non-olfactory  pallium  (neopallium) .  The  latter  appears  first  in  the  lateral 
dorsal  portion  of  the  pallial  wall  and  by  its  subsequent  development  the  archi- 
pallial  wall  is  rolled  inward  upon  the  mesial  surface  of  the  hemispheres. 
Further  changes  consist  in  the  extension  caudally  of  this  portion  pari  passu  with 
the  extension  caudally  of  the  neopallium  and  then  the  practical  obliteration 
of  its  middle  portion  by  the  great  neopallial  commissure,  the  corpus  callosum 
(Fig.  408,  G  and  H). 

In  addition  to  the  increasing  projection  of  stimuli  from  all  parts  of  the  body 
upon  the  neopallium  and  the  consequent  increase  in  centripetal  fiber  termina- 
tions and  in  centrifugal  neurone  bodies  lying  in  its  walls,  a  second  factor  in 
the  development  of  the  neopallium  is  the  enormous  increase  of  its  association 
neurones.  It  is  the  latter  feature  which  especially  distinguishes  the  human 
from  other  mammalian  brains. 

The  biological  significance  of  these  changes  lies  in  the  fact  that  there  is  thus 
produced  a  mechanism  not  only  for  the  association  of  all  kinds  of  stimuli,  but 


THE  NERVOUS  SYSTEM. 


469 


FIG.  408. — A-F  (Edinger)  are  sagittal  sections  showing  structures  lying  in  the  median  line  and  also 
paired  structures  (e.g.,  pallium)  lying  to  one  side  of  the  median  line.  The  cerebellum  is 
black.  It  is  doubtful  whether  the  membranous  roof  in  A  indicated  as  pallium  is  strictly 
homologous  with  that  structure  in  other  forms.  In  B,  Pallium  indicates  prepallial  structures. 

Aq.  Syl.,  Aquseductus  Sylvii;  Basis  mesen.y  basis  mesencephali;  Bulb,  olf.,  bulbus  olfactorius;  Corp. 
striat.,  corpus  striatum;  Epiph.,  epiphysis;  G.  h.,  ganglion  habenulae;  Hyp.,  hypophysis; 
Infund.,  infundibulum;  Lam.  t.,  lamina  terminalis;  Lob.  elect.,  lobus  electricus;  L.  vagi, 
lobus  vagi;  L.  opt.,  mid-brain  roof;  Med.  obi.,  medulla  oblongata;  Opt.,  optic  nerve;  Pl.chor., 
plexus  chorioideus;  Rec.  inf.,  recessus  infundibuli;  Rec.  mam.,  recessus  mammillaris;  Saccus 
vase.,  saccus  vasculosus;  Sp.  c.,  spinal  cord;  ventr.,  ventricle;  v.  m.  a.,  velum  medullare 
anterius;  v.m.  p.,  velum  medullare  posterius. 

G  and  H  show  the  mesial  surface  of  the  cerebral  hemispheres  in  a  low  (G)  and  high  (H)  Mammal. 
G.  Elliot  Smith,  Edinger,  slightly  modified. 

The  exposed  gray  matter  of  the  olfactory  regions  is  shaded,  the  darker  shade  indicating  the  archi- 
pallium  (preterminal  area  and  hippocampal  formation),  the  lighter  shade  indicating  the 
rhinencephalon,  which  consists  of  the  anterior  and  the  posterior  (principally  pyriform)  olfactory 


470  TEXT-BOOK  OF  EMBRYOLOGY. 

also  for  very  complex  coordinations  between  these  stimuli.  In  this  way  an 
extensive  symbolization  and  formulation  of  individual  experience  (memory, 
language,  etc.)  can  take  place.  The  formulated  experience  of  one  generation 
can  be  immediately  transmitted  (by  education  in  the  broad  sense  of  the  term) 
to  the  plastic  late-developing  neopallia  of  the  next  generation.  In  this 
way  a  racial  experience  may  be  rapidly  built  up  without  the  direct  inter- 
vention of  the  slow  processes  of  heredity  and  natural  selection  and  each  gen- 
eration profit  by  the  accumulated  experience  of  past  generations  to  a  much 
greater  extent.  The  nervous  mechanism,  the  pallium,  is  provided  by  in- 
heritance; experience  is  not  inherited  but  "  learned."  The  pallial  associative 
mechanisms  are  continuously  modified  by  their  activities,  thus  affecting  the 
character  of  subsequent  pallial  reactions  (associative  memory).  Such  reac- 
tions are  usually  termed  psychical  or  conscious,  as  distinguished  from  the 
reflex  reactions  of  other  parts  of  the  nervous  system. 

In  the  course  of  these  developments  the  pallium  or  cerebral  hemispheres 
have  enormously  increased  in  size  until  in  man  they  overlap  all  the  other  parts 
of  the  brain.  Naturally  the  extensive  connections  of  the  neopallium  with  the 
rest  of  the  brain  have  profoundly  modified  the  latter.  Among  the  new  struc- 
tures which  have  on  this  account  been  added  to  the  older  structures  of  the  rest  of 
the  brain,  the  following  may  be  mentioned:  (i)  The  centripetal  connections  of 
the  neopallium,  consisting  mainly  of  what  are  usually  termed  the  thalamic  radi- 
ations. These  consist  essentially  of  a  system  of  neurones  passing  from  the 
above  mentioned  termini  in  the  thalamus  of  general  somatic,  acoustic  and  optic 
ascending  systems  to  certain  areas  in  the  cerebral  hemispheres.  In  this  system 
we  can  distinguish  (a)  the  continuation  of  the  fillet  (general  somatic)  to  the  cen- 
tral region  (somaesthetic  area)  of  each  hemisphere;  (b)  the  optic  radiation  from 
the  lower  thalamic  optic  center  (lateral  geniculate  body)  to  the  calcarine 
(visual)  area  of  the  hemisphere;  (c)  the  acoustic  radiation  from  the  medial 
geniculate  body  of  the  thalamus  to  the  upper  temporal  region  (auditory  area) 
of  the  hemisphere.  Associated  with  these  last  two  connections  are  the  increase 

lobes.  In  Amphibia  and  Reptiles  the  hippocampal  formation  includes  all  or  nearly  all  of  the 
mesial  surface.  As  the  early  neopallium  appears  in  the  lateral  hemisphere  walls,  the  neo- 
pallial  commissural  fibers  first  pass  across  the  median  line  in  the  ventral  or  anterior  com- 
missure. With  the  increase  of  the  neopallium  and  its  extension  on  the  mesial  hemisphere 
walls,  its  commissural  fibers  pass  across  more  dorsally  via  the  archipallial  or  fornix  com- 
missure (psalterium)  forming  the  neopallial  commissure  or  corpus  callosum,  the  great  de- 
velopment of  which  nearly  obliterates  the  anterior  hippocampal  formation. 

Com.  ant.,  Anterior  commissure;  corp.  callosum,  corpus  callosum;  Fimbr.,  fimbria;  Fiss.  hippo- 
campi, hippocampal  fissure;  Lam.  t.,  lamina  terminalis;  Lob.  olf.  ant.,  anterior  olfactory  lobe; 
Lob.  pyriformis,  pyriform  lobe;  Psalt.,  psalterium  (fornix  commissure);  Sept.  pell.,  septum 
pellucidum;  Tub.  olf.,  tuberculum  olfactorium.  Only  a  part  of  the  gray  (cortex)  of  the  hip- 
pocampal formation  appears,  as  the  gyrus  dentatus,  on  the  mesial  surface;  the  remainder  forms 
an  eminence,  the  cornu  Ammonis,  on  the  ventricular  surface.  This  invagination  is  indicated 
externally  by  the  hippocampal  fissure.  The  exposed  fiber  bundle  forming  the  edge  of  this 
formation  (fimbria)  passes  forward  (fornix  and  its  commissure)  and  thence  descends,  as  the 
anterior  pillar  of  the  fornix,  behind  the  anterior  commissure.  The  anterior  pillar  is  partly 
indicated  by  a  few  lines  in  this  region  in  the  figure. 


THE  NERVOUS  SYSTEM. 


471 


FIG.  409. — Principal  afferent  and  efferent  suprasegmental  pathways  (excepting  the  archipallial  con- 
nections, the  efferent  connections  of  the  mid-brain  roof  and  the  olivo-cerebellar  connections). 
Neopallial  connections  are  indicated  by  broken  lines.  Intersegmental  connections  are  omitted. 
Some  peripheral  elements  are  indicated.  Each  neurone  group  (nucleus  and  fasciculus)  is  in- 
dicated by  one  or  several  individual  neurones.  Decussations  of  tracts  are  indicated  by  an  X. 

OC.,  Acoustic   radiation,  from  medial  geniculate  body  to  temporal  lobe;  br.  con].,  brachium  con- 


472  TEXT-BOOK  OF  EMBRYOLOGY. 

of  the  geniculate  bodies  and  the  diminution  of  the  mid-brain  in  importance 
already  alluded  to  (p.  467).  (2)  The  centrifugal  connections  consisting  of  (a) 
the  pyramids  passing  from  the  precentral  area  of  each  hemisphere  to  various 
lower  efferent  neurones,  or  neurones  affecting  the  latter,  and  forming  part  of  the 
internal  capsule  and  pes  pedunculi ;  (b)  fibers  from  various  parts  of  the  hemis- 
phere, forming  the  greater  part  of  the  rest  of  the  internal  capsule  and  pes,  and 
terminating  principally  in  the  pontile  nuclei  whence  a  continuation  of  this 
system  (the  fibers  of  the  middle  peduncle),  passes  to  the  cerebellar  hemisphere. 
The  great  increase  in  size  of  the  cerebellar  hemispheres,  of  the  contained 
nuclei  dentati,  and  probably  of  the  superior  cerebellar  peduncles  are  further 
effects  of  this  new  connection,  which  has  already  been  alluded  to  (see  Cere- 
bellum, p.  466),  (Fig.  409.) 

Another  important  effect  of  the  development  of  the  pallium  is  the  assump- 
tion by  man  of  the  upright  position,  due  both  to  the  specialization  of  the 
hand  to  execute  pallial  coordinations  and  its  consequent  release  from  locomo- 
tion, and  also  to  the  overhanging  of  the  eyes  by  the  enlarged  cranium.  The 
great  increase  of  cerebellar  connections  may  be  partly  due  to  the  new 
problems  of  equilibrium  connected  with  the  upright  position. 

GENERAL  DEVELOPMENT  OF  THE  HUMAN  NERVOUS  SYSTEM  DURING 

THE  FIRST  MONTH. 

One  of  the  earliest  stages  in  the  development  of  the  human  nervous  system 
is  shown  in  the  2  mm.  embryo  of  about  two  weeks  (Fig.  410).  This  shows 
the  stage  of  the  open  neural  groove.  The  appearance  of  a  transverse  section 
of  the  neural  plate,  groove  and  folds,  in  other  forms,  is  shown  in  Figs.  411 
and  412. 

The  neural  folds  now  become  more  and  more  elevated  and  finally  meet,  thus 
forming  the  neural  tube  as  previously  described  (p.  451).  The  fusion  of  the 
neural  folds  begins  in  the  middle  region  and  thence  extends  cranially  and  cau- 

junctivum  (superior  cerebellar  peduncle);  brack,  pon.,  brachium  pontis  (middle  cerebellar 
peduncle);  b.  q.  i.,  brachium  quadrigeminum  inferias  (a  link  in  the  cochlear  pathway) ;  c.  g.  I., 
lateral  or  external  geniculate  body;  c.g.m.,  medial  or  internal  geniculate  body;  c.qitad.,  cor- 
pora quadrigemina;  f.cort.-sp.,  cortico-spinal  fasciculus  (pyramidal  tract);/,  c.  p.-f.  frontal 
cortico-pontile  fasciculus  (from  frontal  lobe);  f.c.-p.t.,  temporal  cortico-pontile  fasciculus 
(from  temporal  lobe);  /.  c.-p.o.,  occipital  cortico-pontile  fasciculus  (from  occipital  lobe); 
f.cun.,  fasciculus  cuneatus  (column  of  Burdach);  f.grac.,  fasciculus  gracilis  (column  of 
Goll) ;  /.  s.-t.,  tract  from  cord  to  mid-brain  roof  and  thalamus  (sometimes  included  in  Gowers* 
tract);  f.sp.-c.d.,  dorsal  spino-cerebellar  fasciculus  (tract  of  Flechsig);  f.sp.-c.v.,  ventral 
spino-cerebellar  fasciculus  (tract  of  Gowers,  location  of  cells  in  cord  uncertain);  lem.  lat., 
lateral  lemniscus  or  lateral  fillet;  lemniscus1  med.,  medial  lemniscus  or  fillet  (the  part  to  the 
thalamus  is  mainly  a  neopallial  acquisition);  n.coch.,  cochlear  nerve;  n.  cun.,  (terminal) 
nucleus  of  the  column  of  Burdach;  n.grac.,  nucleus  of  the  column  of  Goll;  n.dent.,  nucleus 
dentatus;  n.  opt.,  optic  nerve;  n.r.,  nucleus  ruber  (red  nucleus);  pes  ped.,  pes  peduncu'.i 
(crusta);  pulv.  thai.,  pulvinar  thalami;  Pyr.,  pyramid;  rod.  ant.y  ventral  spinal  root;  rod.  post,. 
dorsal  spinal  root;  rod.  opt.,  optic  radiation  (from  lateral  geniculate  body,  and  pulvinar  ( ?), 
to  calcarine  region) ;  somaes.,  bundles  from  thalamus  to  postcentral  region  of  neopallium; 
s p. gang.,  spinal  ganglion;  thai.,  thalamus. 


THE  NERVOUS  SYSTEM.  473 

dally.  The  stage  of  partial  closure  of  the  neural  tube  is  shown  in  Eternod's 
figure  of  a  human  embryo  of  2.1  mm.  (Fig.  413,  b).  This  order  of  closure  in- 
dicates, to  some  extent,  the  order  of  subsequent  histological  development;  the 
extreme  caudal  and  cephalic  extremities  are  more  backward  than  the  parts 
which  close  first.  The  last  point  to  close  anteriorly  marks,  as  stated  previously 
(p.  451),  the  cephalic  extremity  of  the  neural  tube  and  is  the  anterior  neuropore. 
As  indicated  in  Eternod's  embryo,  the  anterior  end  of  the  neural  plate  is  broader 
even  before  its  closure;  thus  when  the  tube  is  completed  its  anterior  end  is  more 
expanded.  This  expansion  is  the  future  brain,  the  narrower  caudal  portion 


Yolk  sac 


Amnion 


Neural  groove 


Neurenteric 
canal 


Belly  stalk 


Chorion 

FIG.  410. — Dorsal  view  of  human  embryo,  two  millimeters  in  length,  with  yolk  sac. 

von  Spee,  Kollmann. 
The  amnion  is  opened  dorsally. 

being  the  future  spinal  cord.  Before  the  closure  of  the  brain  part  of  the  tube 
the  beginnings  of  the  three  primary  brain  vesicles  are  also  indicated  (Fig.  120). 
At  this  stage  the  neural  plate  shows  no  differentiation  into  nervous  and  sup- 
porting elements.  The  neural  tube  is  composed  of  the  two  lateral  walls  and 
the  median  roof  and  floor  plates  (comp.  p.  453)  (Figs.  345  and  442). 

The  appearance  of  the  anterior  end  of  the  neural  tube  with  the  closure  com- 
pleted, except  the  anterior  and  posterior  neuropores,  is  shown  in  the  model  of 
one  half  of  the  tube.  The  external  appearance  and  also  the  inner  surfaces  are 
shown  in  Figs.  414  and  415.  At  this  stage  the  cephalic  flexure  (see  p.  454)  is 
already  quite  pronounced,  the  cephalic  end  of  the  brain  tube  being  bent  ven- 


474 


TEXT-BOOK  OF  EMBRYOLOGY. 


trally  at  about  a  right  angle  to  the  longitudinal  axis  of  the  remaining  portion  of 
the  tube.  This  bending  begins  before  the  closure  of  the  cephalic  part  of  the 
neural  tube  (Fig.  120).  From  each  side  of  the  brain  near  the  cephalic  ex- 
tremity is  an  evagination  of  the  brain  wall,  the  beginning  of  the  optic  'vesicles. 


Ectoderm 


Mesoderm 


x       Chorda  anlage  Entoderm 

FIG.  411. — Transverse  section  through  dorsal  part  of  embryo  of  frog  (Rana  fusca). 
x,  Groove  indicating  evagination  to  form  mesoderm. 


Ziegler. 


The  process  of  evagination  and  consequently  the  location  of  the  vesicle  begins 
before  the  closure  of  the  tube. 

Dorsal  and  anterior  to  the  optic  vesicles  can  be  seen  a  slight  unpaired  pro- 
trusion of  the  dorsal  wall,  the  beginning  of  the  pallium.     The  area  basal  to  it  and 


Prim.    Intermed. 
seg.      cell  mass 


Parietal  and 
visceral  mesoderm 


Chordal 
plate 


Coelom         Entoderm       Blood  vessels 
FIG.  412. — Transverse  section  of  dog  embryo  with  ten  pairs  of  primitive  segments.     Bonnet. 

extending  a  short  distance  into  the  anterior  wall  of  the  optic  vesicle  is  the  site  of 
the  future  corpus  striatum  (Figs.  414  and  415). 

Caudal  to  the  pallium  and  separated  from  it  by  a  slight  constriction  (in- 
dicated best  by  the  ridge  on  the  inner  wall)  is  another  protrusion  of  the  dorsal 
wall,  the  roof  of  the  diencephalon.  Still  further  caudally  and  separated  from  the 


THE  NERVOUS  SYSTEM. 


475 


roof  of  the  diencephalon  by  another  slight  constriction  is  another  expansion  of 
the  dorsal  wall,  the  roof  of  the  mid-brain  or  of  the  mesencephalon  which  arches 
over  the  cephalic  flexure.  It  is  separated  by  another  constriction  (plica 
rhombo-mesencephalica)  from  the  rhombic  brain  or  rhombencephalon,  which  latter 
tapers  into  the  cord.  A  ventral  bulging  of  the  rhombencephalon  indicates  the 
future  pons  region  (Figs.  414  and  415). 


Heart 


Ant.  entrance  to 
prim,  gut  (Ant. 
"Darmpforte") 


Post,  entrance  to 
prim,  gut  (Post. 
"Darmpforte") 


Cerebral  plate 


Amnion 


Yolk 
(cut  edge) 

Yolk  sac 


Belly  stalk 


Neural  tube 


Primitive 
segment 


Neural  fold 
Neural  groove 


Neural  fold 


FIG.  413.— (a)  Ventral  view;  (6)  dorsal  view  of  human  embryo  with  8  pairs  of  primitive 

segments  (2.11  mm.).     Eternod.    From  models  by  Ziegler. 

In  b  the  amnion  has  been  removed,  merely  the  cut  edge  showing;  in  a  the  yolk  sac  has 

been  removed. 


Even  at  this  early  stage  the  cavity  of  the  caudal  part  of  the  rhombencephalon 
is  expanded  dorsally  due  to  an  expansion  of  the  roof  plate,  which  forms  only  the 
narrow  dorsal  median  part  of  the  rest  of  the  tube.  This  expansion  reaches  its 
maximum  about  opposite  the  auditory  vesicle. 

The  principal  changes  in  form  during  the  next  two  weeks  are  the  following 
(Figs.  416  and  472):  The  cephalic  flexure  becomes  still  more  pronounced  so 
that  the  anterior  end  of  the  neural  tube  is  folded  back  upon  the  ventral  side  of 
the  rest  of  the  brain,  an  effect  probably  enhanced  by  the  expansion  of  the 


476 


TEXT-BOOK  OF  EMBRYOLOGY. 


FIG.  414. — Lateral  view  of  the  outside  of  a  model  of  the  brain  of  a  human 
embryo  two  weeks  old.     His. 


Diencephalon 


Pallium 


Mesencephalon 


Rhombq- 
mesencephalic  fold 


Rhombencephalon 


Neuropore 
Corpus  striatum 
P.  f. 
Optic  evagination 


Ventral  cephalic  fold 
(Seesel's  pocket) 


Pons  region 


FIG.  415. — Lateral  view  of  inner  side  of  the  same  model  shown  in  Fig.  414. 
P.f.  is  the  ridge  corresponding  to  the  peduncular  furrow  on  the  outer  side. 


THE  NERVOUS  SYSTEM.  477 

ventral  wall  of  the  anterior  portion  (Figs.  416  and  472).  In  the  space  thus 
enclosed  the  dorsum  sellae  is  subsequently  formed.  Associated  with  this 
increase  of  the  cephalic  flexure  is  an  increased  prominence  of  the  mid-brain 
roof.  The  pontine  flexure  has  begun,  there  being  now  a  bending  of  the  whole 
tube  in  the  pons  region,  the  concavity  of  the  bend  being  dorsal.  At  the  same 
time  there  is  a  corresponding  tendency  for  the  roof  of  the  rhombencephalon  to 
become  shorter  and  wider.  There  is  also  a  further  thinning  of  the  above 
mentioned  expanded  portion  of  the  roof  plate  in  this  region,  and  associated 
with  this  a  thrusting  of  the  thick  lateral  walls  outward  at  the  top  so  that  they 
come  to  lie  almost  flat  instead  of  vertically  as  in  the  cord.  From  the  cord 
to  the  place  of  greatest  width  above  mentioned,  this  dorsal  thrusting  apart 


FIG.  416. — Profile  view  of  a  model  of  the  brain  of  a  human  embryo  during  the  third  week.    His.  \ 
A,  Optic  vesicle;  A.v.,  auditory  vesicle;  Br,  pons  region;  H,  pallium;  Hh.  cerebellum;  J,  isthmus; 
M,  mid-brain;  N  and  /?/,  medulla;  XK,  cervical  flexure;  Pm,  mammillary  region;  2>,  in- 
fundibulum;  Z,  inter-brain  or  diencephalon. 

of  the  lateral  rhombic  walls  obviously  becomes  more  and  more  pronounced. 
In  front  of  this  region  of  greatest  width,  the  roof  plate  becomes  narrower  and 
the  dorsal  parts  of  the  walls  (alar  plates)  form  the  rudiment  of  the  cerebellum, 
the  rest  of  the  rhombic  brain  forming  the  medulla  oblongata.  Each  lateral 
wall  of  the  rhombic  brain  is  now  divided  into  a  dorsal  longitudinal  zone  or 
plate  (alar  plate)  and  a  ventral  zone  or  plate  (basal  plate)  by  a  longitudinal 
furrow  along  its  inner  surface,  the  sulcus  limitans.  A  study  of  the  external 
appearances  and  transverse  sections  of  this  part  of  the  brain  tube  will  make 
these  relations  clear  (Figs.  456,  436  to  439  and  427).  Neuromeres  are  also 
present  at  this  stage  (see  p.  489).  In  the  meantime  the  neural  tube  has  also 
become  bent  ventrally  at  the  junction  of  the  brain  and  cord,  forming  the  cervical 


478  TEXT-BOOK  OF  EMBRYOLOGY. 

flexure.  The  pallium  has  increased  in  size  and  now  forms  a  considerable 
prominence  on  the  brain  tube.  Its  boundaries  are  also  much  more  clearly 
marked  off  (see  Fig.  471).  On  the  inner  side  of  the  tube,  the  area  below 
the  bulging  of  the  pallium  is  the  corpus  striatum.  Externally,  just  below  the 
bulging,  we  have  the  region  where  the  olfactory  lobes  are  differentiated.  The 
proximal  part  of  the  optic  evagination  has  become  longer  and  narrower.  The 
ventral  expansion  of  the  diencephalon  is  the  hypothalamus,  the  portion  of  the 
diencephalon  dorsal  to  the  latter  being  the  thalamus.  Two  slight  protrusions 
of  the  ventral  wall  of  the  hypothalamus  have  appeared;  the  caudal  one  is  the 
mammillary  region,  the  anterior  one  the  infundibulum.  The  cavity  of  the 
diencephalon  (third  ventricle)  is  connected  by  the  mid-brain  cavity  (iter  or 
aquaductus  Svlvii)  with  the  rhombic  brain  cavity  or  iourth  ventricle. 

HISTOGENESIS  OF  THE  NERVOUS  SYSTEM. 

The  neural  plate  is  at  first  a  simple  columnar  epithelium.  The  various 
processes  by  which  this  is  converted  into  the  fully  formed  nervous  system  are : 
(i)  cell  proliferation;  (2)  cell  migration;  (3)  cell  differentiation.  These  proc- 
esses are  not  entirely  successive  in  point  of  time,  but  overlap  each  other.  Cell 
division  is  present  from  the  first,  increases  to  a  certain  period  in  development 
and  then  practically  ceases;  cell  migration  is  partly  a  necessary  concomitant  and 
resultant  of  cell  division,  and  cell  differentiation  is  in  part  due  to  the  growth  of 
the  cytoplasm  and  is  in  part  a  result  of  environmental  differences  produced  by 
these  processes.  In  development  the  following  stages  may  be  distinguished : 

(i)  Stage  of  indifferent  epithelium;  (2)  appearance  of  nerve  elements 
(neurones)  and  resulting  differentiation  into  supporting  and  nerve  elements; 
(3)  growth  of  neurones  and  resulting  differentiation  and  development  of  (a) 
peripheral  neurones,  (b)  lower  intermediate  or  intersegmental  neurones,  (c) 
neurones  of  higher  centers  and  neurone  groups  in  connection  with  them  (supra- 
segmental  neurones).  These  stages  do  not  occur  simultaneously  throughout  the 
whole  neural  tube,  some  parts  being  more  backward  in  development  than  others 
(p.  473).  In  general  the  spinal  cord  and  epichordal  segmental  brain  are  most 
advanced  in  development.  Furthermore,  the  ventral  part  of  the  brain  tube 
precedes  the  dorsal.  The  most  backward  part  of  the  whole  neural  tube  is  the 
pallium. 

The  various  phases  of  /0rw-differentiation  of  the  neurone  are  (i)  the 
development  of  the  axone  and,  later,  of  its  branches;  (2)  the  growth  of  the 
dendrites;  (3)  the  formation  of  accessory  coverings  or  sheaths,  the  neurilemma 
and  the  myelin  (medullary)  sheath.  The  principal  internal  differentiations 
are  (i)  the  appearance  of  the  neurofibrils;  (2)  the  chromophilic  bodies  of 
Nissl;  (3)  pigment.  These  latter  may  all  be  regarded  as  products  of  the 
nucleus  and  undifferentiated  cytoplasm  of  the  nerve-cell. 


THE  NERVOUS  SYSTEM.  479 

Epithelial  Stage.    Development  of  Neuroglia. 

From  the  very  first,  the  neural  plate  exhibits  dividing  cells  similar  to  those 
seen  in  the  non-neural  ectoderm.  The  cell  divisions  are  indirect  and  the 
mitoses  are  confined  to  the  outer  part  of  the  ectoderm,  occurring  between  the 
outer  ends  of  the  resting  epithelial  cells  (Fig.  417).  These  dividing  cells  have 
been  termed  by  His  germinal  cells.  When  the  neural  tube  is  formed,  the 
mitoses  are  still  confined  to  the  outer,  now  the  luminal,  surface,  this  being  a 
general  phenomenon  in  developing  epithelial  tubular  structures.  As  a  result 
the  daughter  nuclei  migrate  away  from  the  lumen. 

In  the  most  advanced  parts  of  the  neural  tube  (see  p.  478),  the  mitoses  in- 
crease in  number  up  to  about  the  fourth  to  sixth  week  of  development,  and  then 
diminish  and  finally  nearly  disappear  about  at  the  end  of  two  months.  At 
about  the  time  the  blood  vessels  penetrate  the  tube,  the  mitoses  .are  no  longer 
entirely  confined  to  the  proximity  of  the  lumen. 

As  a  result  of  proliferation,  the  epithelial  wall  very  early  assumes  the  ap- 
pearance of  a  stratified  epithelium — at  least  there  are  several  strata  of  nuclei. 
There  are  at  this  stage  in  many  forms  two  layers,  an  outer  or  marginal  layer, 
free  of  nuclei,  and  an  inner  or  nuclear  layer  (Figs.  418  and  419).  In  a  human 
embryo,  however,  of  about  two  weeks  this  division  into  layers  is  yet  hardly 
evident,  though  there  are  several  strata  of  nuclei.  Apparently  these  layers  are 
not  well-marked  until  the  radial  arrangement  of  the  myelospongium,  as 
described  below,  has  become  more  pronounced. 

Accompanying  the  above  changes,  changes  also  manifest  themselves  in  the 
character  of  the  cells.  At  about  the  time  of  the  closure  of  the  neural  tube,  the 
cell  boundaries  become  indistinct  and  finally  practically  obliterated,  thus  form- 
ing a  syncytium,  the  myelospongium.  At  the  same  time,  the  syncytium  becomes 
very  alveolar  in  structure  and  a  general  spongioplasmic  reticulum  is  formed  (Figs. 
418  and  419)  by  the  anastomosing  denser  strands  (trabeculae)  of  protoplasm. 
At  a  very  early  stage  (two  weeks),  these  trabeculae  unite  along  the  inner  and 
outer  walls  of  the  neural  tube  forming  internal  and  external  limiting  mem- 
branes. The  nuclei  of  the  neural  tube  have  at  first  an  irregular  arrangement 
in  the  reticulum,  at  least  in  the  human  embryo.  This  is  followed  by  a  more 
radial  arrangement  of  both  nuclei  and  protoplasmic  filaments  (Fig.  420) ,  form- 
ing nucleated  radial  masses  of  protoplasm — the  sponglioblasts  (Figs.  419  to 
422).  There  is  some  dispute  as  to  the  loss,  complete  or  incomplete,  of  identity 
of  the  epithelial  cells  in  the  formation  of  the  spongioblasts.  According  to 
Hardesty,  they  are  formed  by  a  collapse  of  the  epithelial  cells  and  a  rearrange- 
ment of  their  denser  parts  into  axial  filaments.  The  radial  arrangement  does 
not  extend  into  the  outer  part  of  the  neural  tube  which,  retaining  its  irregular 
reticular  character,  is  now  non-nucleated  in  the  human  embryo  and  forms  the 


480 


TEXT-BOOK  OF  EMBRYOLOGY, 


*s:aaf 


a 


FIG.  420. 


FIG.  417. — From  the  neural  tube  of  an  embryo  rabbit  shortly  before  the  closure  of  the  tube,  g,  Germi- 
nal or  dividing  cell;  m,  peripheral  zone,  position  of  the  later  marginal  layer.  His. 

FIG.  418. — Pig  of  5  mm.,  unflexed.  Just  after  closure  of  the  neural  tube.  Segment  of  a  vertical 
section  of  the  lateral  wall  of  the  tube,  g,  Germinal  cells;  m,  beginning  of  marginal  layer; 
mil,  internal  limiting  membrane;  r,  radial  columns  of  protoplasm.  The  resting  nuclei  lie  in 
the  inner  or  nuclear  layer.  Hardesty. 


THE  NERVOUS  SYSTEM. 


481 


marginal  layer.  The  increase  in  the  thickness  and  circumference  of  the  walls 
of  the  tube  and  the  resulting  tensions  may  be  a  factor  in  this  arrangement 
cf  the  protoplasmic  filaments.  At  the  boundary  between  the  marginal  and 
nuclear  layers  the  reticulum  appears  to  be  especially  dense. 

With  the  further  increase  and  development  of  the  nervous  elements  (see 
p.  485)  the  radial  arrangement  of  the  spongioblasts  noted  above  becomes  more 
and  more  obliterated.  As  shown  by  Golgi  preparations,  in  their  migration  from 
the  lumen  (Fig.  422)  the  spongioblasts  lose  their  connection  with  the  lumen, 


mil 


mv 


FIG.  421. — Hardesty.  Combination  drawing  from  sections  of  pig  of  15  mm.  The  upper  part  is 
from  a  section  of  the  same  stage  as  the  lower  but  stained  by  the  Golgi  method.  By  migra- 
tion and  differentiation  the  mantle  layer  has  been  formed.  The  cells  remaining  near  the 
lumen  form  the  ependyma  layer  (ep.).  b,  Boundary  between  mantle  and  marginal  layers; 
ep,  ependyma;  mli  and  mle,  internal  and  external  limiting  membranes;  mv,  differently 
arranged  mid-ventral  portion  of  the  marginal  layer;  r,  radial  filaments;  cs,  connective  tissue 
syncytium. 


their  peripheral  processes  become  abbreviated  and  disappear,  and  they  finally 
differentiate  into  the  irregular  branching  neuroglia  cells  (Fig.  423).  According 
to  Hardesty,  there  is  simply  a  general  nucleated  mass  which  changes  form 
pari  passu  with  changes  in  the  enclosed  differentiating  nervous  elements, 
finally  assuming  shapes  dependent  upon  the  character  of  the  spaces  between 
the  formed  nervous  elements.  An  exception  to  this  is  a  layer  of  nucleated 
elements  which  remain  next  the  lumen  and  form  the  ependyma  cells  which  still 

FIG.  419. — Pig  of   7  mm.,  unflexed.     Segment  from  the  ventro-lateral  wall  of   the  neural  tube; 

g,   Germinal     cells;    mli,  internal    limiting    membrane;    mle,  external  limiting  membrane 

r,  radial,  axial  filaments  of  the  syncytial  protoplasm;  p,  beginning  of  pia  mater.     Hardesty. 
FIG.  420. — Pig  of  10  mm.,  "crown-rump"  measurement.     Segment  from  lateral  wall  of  neural  tube. 

b,  boundary  between    nuclear    layer  and    marginal  layer  (m).     Other   references   same   as 

in  419.     Hardesty. 
a  indicates  the  zone  in  which  the  dividing  cells  are  located.     Later,  it  is  composed  of  the  inner  ends 

of  the  ependyma  cells  (column  layer  of  His). 


482 


TEXT-BOOK  OF  EMBRYOLOGY. 


THE  NERVOUS  SYSTEM. 


483 


send  radial  extensions  into  the  wall  of  the  neural  tube  (Figs.  421  and  422). 
These  cells  develop  cilia  projecting  into  the  lumen. 

A  still  later  differentiation  m  the  supporting  elements  of  the  tube  is  the  ap- 
pearance of  neuroglia  fibers — a  product  of  the  spongioblastic  protoplasm,  but 
differing  from  it  chemically  (Fig.  423).  The  exact  relation  of  these  neuroglia 
fibers  to  the  nucleated  neuroglia  cells  in  the  adult  is  a  matter  of  dispute. 


"  W/^>^3yftl^fE*&^£iM5w5?;d 

.      •  .     .  *          /••         jfSiRSf^ 


B       d       f 


FIG.  423. — Hardesty.  Combination  drawing  from  transverse  sections  of  the  spinal  cord  of  20  cm, 
pig.  Showing  the  first  appearance  of  neuroglia  fibers,  a,  Xeuroglia  cell  as  shown  by  the 
Benda  method  of  staining;  a',  similar  cell  by  the  Golgi  method;  b  and  &',  non-nucleated 
masses;  d,  free  nuclei;  e  and/,  differentiating  neuroglia  fibers;  s,  '"'seal-ring"  cells,  envelop- 
ing myelinating  nerve-fibers. 

With  the  penetration  of  blood  vessels  into  the  neural  tube  a  certain  amount  of 
mesodermal  tissue  is  brought  in.  How  much  of  the  supporting  tissue  of  the 
nervous  system  is  derived  from  the  mesoderm  is  uncertain,  but  it  is  most 
probable  that  it  is  relatively  small  in  amount  and  is  confined  principally  to  the 
connective  tissue  of  the  walls  of  the  blood  vessels. 

Early  Differentiation  of  the  Nerve  Elements. 

It  has  been  seen  that  some  of  the  actively  dividing  cells  (germinal  cells)  at 
first  simply  increase  the  ordinary  epithelial  elements  of  the  tube  which  in  turn 
form  the  myelospongium,  the  spongioblasts  and  finally  the  ependyma  and  the 
neuroglia.  Other  daughter  cells  produced  by  the  division  of  the  germinal  cells 


484 


TEXT-BOOK  OF  EMBRYOLOGY. 


differentiate  into  nerve  cells  as  described  below.  Still  others  probably  migrate 
outward  as  indifferent  cells,  which  later  proliferate  and  form  cells  which  differ- 
entiate into  neuroglia  and  nerve  cells. 

According  to  recent  researches  (Cajal),  by  means  of  the  silver  stain  of  Cajal 
the  first  indication  of  the  differentiation  of  cells  into  nerve  cells  is  the  appear- 
ance of  neurofibrils  in  the  cytoplasm  of  cells  near  the  lumen.  The  part  of  the 
cell  in  which  the  neurofibrils  first  appear  is  called  the  fibrillogenous  zone 
(Held)  and  is  usually  in  the  side  furthest  from  the  lumen.  The  cells  in  which 
these  appear  are  apparently  without  processes,  and  are  accordingly  termed 
apolar  cells  (Cajal).  (Fig.  424.) 


FIG.  424. — Section  through  the  wall  of  the  fore-brain  vesicle  of  a  chick  embryo  of  3  J  days.     Cajal. 

A,  b  and  c,  Differentiating  nerve  cells  in  apolar  stage,  the  neurofibrils  are  black;  a,  cell  in  a  stage 
transitional  to  the  bipolar  stage;  B,  bipolar  cells;  c  (at  lower  right  corner),  cone  of  "growth" 
of  developing  axone;  e,  tangential  axone.  The  cells  in  the  bipolar  stage  have  migrated  out 
ward,  but  the  neuroblast  or  mantle  layer  has  not  yet  been  differentiated. 


The  next  step  in  the  development  of  many,  but  probably  not  all,  of  these  cells 
is  their  transformation  into  bipolar  cells  by  the  outgrowth  of  two  neurofibrillar 
processes,  one  directed  toward  the  lumen,  the  other,  usually  thicker,  toward  the 
periphery,  the  cell  body  at  the  same  time  beginning  to  migrate  outward  (Fig.  424) . 
This  bipolar  stage  may  be  regarded  as  conditioned  to  some  extent  by  the  radial 
arrangement  of  the  other  elements,  due  in  turn  partly  to  the  original  epithelial 
structure  and  partly,  possibly,  to  tensions  produced  by  the  growth  of  the  tube. 
It  is  also  interesting  as  recalling  conditions  in  sensory  epithelia  and  in  the 
cerebrospinal  ganglia.  The  bipolar  stage  is  most  common  probably  in  those 
parts  where  the  elements  show  a  radial  arrangement  in  the  adult.  Such  are  the 
layered  cortices  of  the  mid-brain  and  pallium.  Nerve  cells  maintaining  a  con- 
nection, by  central  processes,  with  the  luminal  wall  have  been  described  in  lower 
Vertebrates.  This  connection  may  be  explained  as  due  to  a  persistence  of  the 
central  processes  of  cells  in  the  bipolar  stage. 


THE  NERVOUS  SYSTEM.  485 

The  next  stage  is  a  monopolar  stage  produced  by  the  atrophy  of  the  luminal 
process.  Cells  in  this  stage  are  the  neuroblasts  of  His,  the  peripheral  processes 
being  the  developing  axones  (Fig.  425).  As  seen  in  ordinary  stains,  the  above 
differentiation  of  the  neuroblasts  is  marked  by  a  corresponding  differentiation 
of  the  nuclear  layer  into  an  inner  layer  retaining  its  previous  characteristic  radial 
arrangement,  and  an  outer  layer  characterized  by  fewer  nuclei  more  irregularly 
arranged.  The  latter  layer  is  the  mantle,  or  neurone  layer  (Fig.  442) .  There 
are  now  three  layers:  (i)  inner  (nuclear),  (2)  mantle  (neurone)  and  (3)  marginal. 
The  mantle  layer  is  thus  produced  by  the  migration  and  differentiation  of  cells 
into  neuroblasts.  While  this  process  may  begin  near  the  lumen  (apolar  nerve 


FIG.  425. — Dorsal  portion  of  the  lumbar  cord  of  a  chick  embryo  of  three  days.     Cajal. 
A,  B,  Cells  in  the  apolar  stage  with  fibrillogenous  zones;  B  shows  transition  to  the  bipolar  stage; 
E,  further  advanced  bipolar  cell;  G,  cells  in  monopolar  stage  or  neuroblasts  of  His;  a,  giant 
cone  of  growth.     These  cells  have  migrated  to  the  outer  part  of  the  nuclear  layer,  thereby 
forming  the  beginning  of  the  mantle  layer. 

cell  of  Cajal)  and  progress  as  the  cell  has  moved  somewhat  further  away  (bipolar 
stage),  the  monopolar  stage  is  probably  reached  only  when  such  cells  form  a  part 
of  the  mantle  layer.  In  other  words,  the  mantle  layer  is  created  by  the  migra- 
tion to  a  certain  location  and  differentiation  to  a  certain  stage  of  the  primitive 
nerve  cells.  The  mantle  layer,  as  previously  stated,  probably  also  contains 
indifferent  cells  which  may  by  further  proliferation  and  subsequent  differentia- 
tion become  either  glia  or  nerve  cells.*  The  looser  arrangement  of  the  cells  of  the 
mantle  layer  is  probably  in  some  measure  due  to  the  growth  of  the  dendrites  which 
appear  soon  after  the  axones.  It  may  be  also  due  to  the  beginning  vascularization 
of  the  tissues  with  resulting  transudates  (His)  which  usually,  however,  begins 
somewhat  later.  The  association  in  time  of  vascularization  and  further  growth 

*  It  is  an  open  question  as  to  how  late  in  development  these  "  extra  ventricular  "  cell- divisions,  in- 
volving "  indifferent "  cells,  may  occur.  The  neuroglia  cells,  however,  like  other  supporting  elements, 
preserve  this  capacity  of  division  indefinitely,  as  shown  by  the  increase  in  neuroglia  cells  in  patho- 
logical conditions. 


486 


TEXT-BOOK  OF  EMBRYOLOGY. 


of  neurocytoplasm  (dendrites)  is  significant.  When  the  cell-proliferation  near 
the  lumen  has  ceased,  the  supply  of  new  cells  ceases,  and  as  the  cells  of  the 
inner  layer  continue  to  differentiate  into  cells  of  the  mantle  layer,  the  inner 
layer,  being  no  longer  replenished  from  within,  is  reduced  to  the  single  layer  of 
cells  which  remain  behind  as  ependyma  cells  (p.  481). 

Differentiation  of  the  Peripheral  Neurones  of  Cord  and 
Epichordal  Segmental  Brain. 

Efferent  Peripheral  Neurones.  The  differentiation  of  a  mantle  or 
neurone  layer  from  the  outer  part  of  the  original  nuclear  layer  is  practically 
universal  throughout  the  whole  neural  tube.  It  appears  first  and  is  conse- 
quently most  advanced,  however,  in  the  ventral  part  of  the  lateral  walls  of  the 
cord  and  epichordal  brain.  The  axones  of  neuroblasts  occupying  the  basal  plate 
of  this  region  of  the  neural  tube  grow  out  through  the  external  limiting  mem- 


FIG.  426. — Ventral  part  of  wall  of  lumbar  cord  of  70- hour  duck  embryo,  showing  efferent  root 

fibers  first  emerging  from  cord  (combined  from  two  sections) .     Cajal. 
A,  Spinal  cord;  B,  perimedullary  space;  C,  meningeal  membrane;  a,  b,  cones  of  radially  directed 

axones;  c,  d,  cones  of  transversely  directed  axones;  D,  bifurcated  cone;  E,F,  cones  crossing 

perimedullary  space;  G,  aberrant  cones. 


brane  and  emerge  as  the  efferent  ventral  root  fibers.  The  appearance  of  these 
early  root  fibers  in  the  duck  is  shown  in  Fig.  426.  The  process  is  similar  in 
the  human  embryo  and  begins  about  the  third  week.  The  neurones  thus 
differentiated  are  the  efferent  peripheral  neurones. 

In  some  forms,  at  least,  cells  appear  to  migrate  out  from  the  tube  along  with 
the  efferent  root  fibers.  Their  fate  is  not  certain,  but  they  probably  either 
metamorphose  into  the  neurilemma  cells  or  possibly  form  part  of  the  sympa- 
thetic ganglia  (see  p.  492).  In  general  the  questions  affecting  the  differentiation 


THE  NERVOUS  SYSTEM. 


487 


of  the  efferent  fibers  are  the  same  as  for  the  afferent  and  are  further  dealt 
with  later  (pp.  492-495). 

The  majority  of  the  efferent  root  fibers  pass  to  the  differentiating  somatic 
muscles  which  they  innervate,  forming  specialized  terminal  arborizations  (the 
motor  end  plates).  The  fibers  to  the  dorsal  musculature  form,  together  with 
the  afferent  fibers  (p.  490),  the  dorsal  branch  of  the  peripheral  spinal  nerve ; 
others  form  part  of  the  ventral  branch  which  sends  a  branch  mesially  toward 
the  aorta.  Some  of  the  fibers  of  the  mesial  branch  take  a  longitudinal  course. 
This  mesial  branch  is  the  white  ramus  communicans  and  terminates  in  the 
various  sympathetic  ganglia  which  are  later  formed  along  its  course  (p.  491). 


FIG.  427. — Diagram  (lateral  view)  of  the  brain  of  a  10.2  mm.  human  embryo  (during  the  fifth  week), 
showing  the  roots  of  the  cranial  nerves.  His. 

Ill,  Oculomotor;  IV,  Trochlear;  V,  Trigeminus  (m,  efferent  root,  s,  afferent  root);  VI,  Abducens; 
VII,  Facial;  VIII,  Acoustic  (c,  cochlear  part,  v,  vestibular  part);  IX,  Glossopharyngeus; 
X,  Vagus;  XI,  Spinal  accessory;  XII,  Hypoglossus.  ot.,  Auditory  vesicle;  Rh.l.,  rhombic 
lip.  The  two  series  of  efferent  roots  (medial  and  lateral)  are  clearly  shown. 


(Comp.  Figs.  263,  265,  432  and  404.)  The  fibers  to  the  sympathetic  ganglia 
are  the  visceral  (splanchnic)  fibers  of  the  ventral  root.  There  are  a  few  other 
fibers  which  grow  dorsally  from  neuroblasts  in  the  ventro-lateral  walls  of  the 
cord  and  thence  out  vio_the  dorsal  root  (Fig.  430) .  They  also  are  probably 
visceral. 

In  the  cord  the  splanchnic  fibers,  writh  the  exception  above  noted,  issue  with 
the  somatic  fibers  in  a  common  ventral  root.  In  the  epichordal  segmental  brain, 
however,  there  is  a  differentiation  of  the  efferent  neuroblasts  of  the  basal  plate 
into  two  series  of  nuclei,  a  medial  and  a  lateral.  The  medial  series  consists  of 


488 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  nuclei  of  the  XII,  VI,  IV  and  III  cranial  nerves,  and  their  axones  grow 
out  as  medial  ventral  root  fibers  (except  the  IV)  (Fig.  427)  to  the  differenti- 
ating muscles  of  the  tongue  and  eyeball  which  they  respectively  innervate. 
These  muscles  are  probably  somatic  and  their  nerves  are  the  somatic  efferent 
cranial  nerves  corresponding  with  the  greater  part  of  the  fibers  of  the  ventral 
roots  of  the  cord  (compare  p.  462).  The  lateral  series  consists  of  the  nuclei  of 
the  efferent  portions  of  the  roots  of  the  XI,  X,  IX,  VII  and  V  cranial  nerves 
and  their  axones  grow  out  as  lateral  roots  (Fig.  427)  to  the  differentiating 
striated  branchial  (splanchnic)  muscles  (sternocleidomastoideus,  trapezius, 


N.triqem.  (motor) 


--N.focialis 

-;-  N.aeusticus 
--------  N.abducens 


-----  N.glo3jqpharyf\g.( 
—  N.  vaguj 


N.hypoglo3sus 


FIG.  428. — Diagram  of  the  floor  of  the  4th  ventricle  of  a  10  mm.  human  embryo,  illustrating  the 
rhombic  grooves  and  their  relations  to  the  cranial  nerves.  The  point  of  attachment  of  the 
acoustic  and  the  sensory  root  of  the  trigeminal  nerve  is  shown  by  dotted  circles;  the  motor 
nuclei  are  represented  by  heavy  dots.  Streeter. 

pharynx,  larynx,  face  and  jaw)  and  also  to  muscles  of  the  viscera  (via  sympa- 
thetic?). The  lateral  nuclei  and  their  roots  are  thus  splanchnic.  (Cf.  pp. 
302-3,  462,  464.)  Their  root  fibers,  with  the  incoming  afferent  fibers,  form  the 
mixed  roots  of  these  nerves.  The  positions  of  these  various  nuclei  and  their 
roots  are  clearly  indicated  in  Figs.  427,  436-439,  447  and  451  and  require  no 
further  description.  Additional  details  are  mentioned  in  connection  with 
the  afferent  cranial  nerves.  In  the  region  of  the  vagus  nerve,  there  are 
differentiated  two  series  of  lateral  nuclei,  a  ventro-lateral  (nucleus  ambiguus  X) 
and  a  dorso-lateral  (dorsal  efferent  nucleus  X)  (comp.  Fig.  407).  Fig.  452 


THE  NERVOUS  SYSTEM. 


489 


apparently  indicates  the  beginning  of  this  differentiation.  The  significance 
of  the  dorso-lateral  nucleus  is  uncertain.  It  possibly  sends  fibers  to  the 
sympathetic  system. 

At  about  this  period  six  transverse  rhombic  grooves  are  plainly  marked  in 
the  floor  of  the  fourth  ventricle,  standing  in  relation  with  the  nerves  of  this 
region  (Fig.  428).  They  are  ordinarily  regarded  as  neuromeric,  but  the  above 
relation  would  indicate  that  they  have  primarily  a  branchiomeric  character 
(Streeter).  It  will  be  noticed  that  each  of  the  three  main  ganglionic  masses 
of  this  region  (p.  495)  corresponds  to  two  of  the  grooves.  (Comp.  p.  465). 

The  further  development  of  the  efferent  neurones  exhibits  phases  common 
to  many  other  nerve-cells  with  a  large  amount  of  cytoplasm  (somatochrome 
cells).  The  further  development  of  the  neuro fibrils  of  cell  body  and  dendrites 

Neural  crest 


Ectoderm 

Neural  crest 

c 

-^'Primitive 
segment 

FIG.  429. — Three  stages  in  the  closure  of  the  neural  tube  and  formation  of  the  neural  crest  (spinal 
ganglion  rudiment).  From  transverse  sections  of  a  human  embryo  of  2.5  mm.  (13  pairs  of 
primitive  segments,  14-16  days),  von  Lenhossek. 

is,  according  to  some  observations,  at  first  confined  to  the  peripheral  portions, 
leaving  a  clear  zone  in  the  vicinity  of  the  nucleus.  The  chromophilic  sub- 
stance first  appears  as  distinct  granules  about  the  end  of  the  second  month, 
there  being  apparently  a  diffuse  chromophilic  substance  present  before  this 
period.  The  chromophilic  granules  also  are  first  differentiated  in  the  per- 
ipheral portions  of  the  cell.  A  still  later  differentiation  is  the  pigment,  which 
probably  does  not  appear  till  after  birth.  This  increases  greatly  in  amount 
in  later  years  and  is  then  an  indication  of  senility  of  the  nerve-cell. 

Afferent  Peripheral  and  Sympathetic  Neurones. — It  has  already  been 
mentioned  (p.  451)  that  in  the  closure  of  the  neural  tube  certain  cells  forming 
an  intermediate  band  between  the  borders  of  the  neural  plate  and  the  non- 
neural  ectoderm  are  brought  together  by  the  fusion  of  the  lips  of  the  plate 


490 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  form  a  ridge  on  the  dorsal  surface  of  the  neural  tube,  this  ridge  being 
known  as  the  neural  crest  (Fig.  429). 

In  the  SPINAL  CORD,  at  three  weeks,  the  neural  crest  has  separated  from  the 
cord  and  split  into  two  longitudinal  bands.  The  ventral  border  of  each  band 
shows  a  transverse  segmentation  into  rounded  clumps  of  cells,  forming  the 
rudiments  of  the  spinal  ganglia  which  later  become  completely  separated.  The 
efferent  roots  have  begun  to  develop  but  the  afferent  roots  appear  later  (fourth 
week,  Fig.  434).  The  cells  composing  these  rudiments  are  polyhedral 
or  oval  rather  than  columnar  and  proliferation  still  proceeds  among  them 
A  differentiation  of  these  cells  soon  begins.  Some,  usually  larger  cells 


FIG.  430. — Part  of  a  transverse  section  through  the  cord  and  spinal  ganglion  of  a  56-hour  chick 

embryo  (combined  from  two  sections) .     Cajal. 
A,  Efferent  cell  of  dorsal  root;  B,  cone  of  growth  of  central  process  (afferent  dorsal  root  fiber)  of 

spinal  ganglion  cell;  C,  bifurcation  of  afferent  root  fibers  in  cord,  forming  beginning  of  dorsal 

funiculus  or  dorsal  white  column  of  cord. 

begin  to  assume  a  bipolar  shape.  Their  central  processes  grow  toward  the 
dorsal  part  of  the  lateral  walls  (alar  plate)  of  the  neural  tube  which  they  enter 
(Fig.  430),  becoming  afferent  (dorsal)  root  fibers.  These  fibers  enter  the  mar- 
ginal layer  and  there  divide  (Figs.  430  and  441)  into  ascending  and  descend- 
ing longitudinal  arms  which  constitute  the  beginning  of  the  dorsal  (posterior) 
juniculus  of  the  cord.  The  peripheral  processes  of  the  developing  ganglion 
cells  grow  toward  the  periphery,  uniting  with  the  ventral  root  and  forming 
with  it  the  various  branches  of  the  peripheral  spinal  nerve  (compare  Figs. 
263,  265,  432  and  404).  Other  peripheral  branches  pass  as  a  part  of  the 
white  ramus  communicans  to  the  sympathetic  ganglia  through  which  they 


THE  NERVOUS  SYSTEM. 


491 


proceed  to  the  visceral  receptors.  These  latter  fibers  are  thus  visceral  afferent 
fibers. 

It  is  now  known  that  the  spinal  ganglion  is  a  much  more  complicated  struc- 
ture and  has  more  forms  of  nerve  cells  than  was  formerly  realized.  The  dif- 
ferentiation into  these  various  types  has  not  yet  been  fully  observed.  The 
bipolar  cells,  however,  become  unipolar  in  the  manner  shown  in  Fig.  431. 
The  cell  body  first  becomes  eccentrically  placed  with  reference  to  the  two  proc- 
esses and  then,  as  it  were,  retracts  from  them,  remaining  connected  with  them 
by  a  single  process.  This  change  may  economize  space. 

According  to  most  authorities,  many  of  the  cells  of  the  neural  crest  do  not 
cease  their  migration  by  forming  spinal  ganglia,  but  undifferentiated  cells 


FIG.  431. — Section  of  spinal  ganglion  of  1 2-day  chick  embryo.     Cajal. 

Showing  various  stages  of  the  change  from  the  bipolar  to  the  unipolar  condition.  A,B,  Unipolar 
cells;  C,  D,  F,  G,  cells  in  transitional  stage;  E,  bipolar  cell;  H,  immature  cell.  The  neuro- 
fibrils  are  well  shown. 


wander  still  further  ventralward  and  form,  probably  also  undergoing  still 
further  proliferation,  the  rudiments  of  the  various  sympathetic  ganglia,  becom- 
ing subsequently  differentiated  into  the  sympathetic  cells.  By  this  migration 
there  is  first  formed  a  longitudinal  column  of  cells  ventral  to  the  spinal  ganglia 
(Fig.  433)  and,  later,  in  relation  with  the  white  communicating  rami  (Fig. 
432).  This  column  becomes  segmented  (seventh  week),  forming  ultimately 
the  ganglia  of  the  vertebral  sympathetic  chain.  In  the  meanwhile,  the 
cells  of  the  column  proliferate  in  places,  forming  rudiments  which,  by  migra- 
tion and  further  differentiation,  form  the  ganglia  of  the  various  prevertebral 
sympathetic  plexuses  (cardiac,  cceliac,  pelvic,  etc.).  Further  migrations  lead  to 
the  formation  of  the  ganglia  of  the  peripheral  plexuses  (Auerbach,  Meissner, 


492 


TEXT-BOOK  OF  EMBRYOLOGY. 


etc.).  All  these  ganglia,  probably,  are  innervated  by  fibers  from  the  white 
ramus,  along  whose  course  they  apparently  migrated.  The  axones  of  their 
cells  pass  to  visceral  structures  either  in  the  same  segment  or,  via  the  longi- 
tudinal chain,  to  those  of  other  segments.  Some  also  join  the  branches  of 
the  peripheral  spinal  nerves  (gray  ramus).  Fibers  of  the  white  ramus  also  pass 
longitudinally  in  the  chain  to  vertebral  ganglia  of  other  segments.  The 
possibility  previously  mentioned  (p.  486)  of  a  contribution  to  the  sympa- 
thetic ganglia  by  cells  migrating  out  along  with  the  ventral  roots  must  be  kept  in 
mind.  It  would  seem  a  priori  more  probable  that  these  latter  would  furnish 
the  efferent  sympathetic  cells,  but  the  efferent  cells  predominate  in  the  sym- 


Spinal  cord  — 
Spinal  ganglion 

Ventral  root  — 

Mixed  spinal  nerve  — 
Myotome  — 

Sympathetic  ganglion ;§§ 


FIG.  432. — From  a  transverse  section  of  a  chick  embryo  of  4^  days.     Neumayer. 


pathetic  and  must  thus  be  regarded  as  derived  partly  or  wholly  from  the 
neural  crest  which  furnishes  at  least  the  major  part  of  all  the  sympathetic 
cells. 

It  seems  probable  that  not  all  the  cells  of  the  neural  crest  form  nerve  cells, 
but  some,  usually  smaller  cells,  become  closely  applied  to  the  spinal  ganglion 
cells,  forming  amphicytes,  while  others  (lemmocytes)  wander  out  along  the  nerve 
fibers  and  become  the  neurilemma  cells,  forming  the  neurilemma.  These  cells 
in  this  case  would  be  quite  strictly  comparable  to  the  glia  cells  of  the  neural 
tube.  According  to  another  view,  the  neurilemma  cells  are  of  mesodermal 
origin.  While  this  point  cannot  be  considered  entirely  determined,  it  seems 
fairly  certain  that  in  some  types  at  least  the  former  view  is  correct,  removal  of 
the  neural  crest  having  resulted  in  the  formation  of  efferent  nerves  without 


THE  NERVOUS  SYSTEM.  493 

neurilemma  cells  (Harrison).  The  modification  into  neurilemma  cells  seems 
to  be  accomplished  by  their  enveloping  the  axones  and  becoming  closely 
applied  to  them. 

The  peripheral  nerve  grows  toward  the  periphery  as  a  bundle  of  fibers  which  forms,  as 
seen  in  many  stains,  a  common  fibrillated  mass,  dividing  at  its  extremity  into  the  develop- 
ing branches  of  the  nerve.  The  lemmocytes  closely  envelop  each  of  these  growing  tips, 
but  proximally  only  envelop  the  main  nerve  trunk  (Bardeen).  The  final  clear  separation  of 


~^»Spinal  ganglion  rudiment 

mm 


/ 

I   </*S     I 

Notochord  ^  ^"( 


^^--Sympathetic  ganglion  rudiment 


FIG.  433. — From  a  transverse  section  through  a  shark  (Scyllium)  embryo  of  15  mm.,  showing  the 

origin  of  the  sympathetic  ganglion.     Onodi. 

In  mammals  the  cells  are  more  scattered  and  their  origin  from  the  spinal  ganglion 
rudiment  not  so  clear. 

the  fibrillated  mass  into  the  individual  nerve  fibers  is  accomplished,  according  to  Gurwitsch, 
by  these  accompanying  cells  forming  septa  within  the  mass  and  finally  enveloping  each 
axone  as  its  neurilemma  sheath.  Growth  in  bundles  appears  to  be  characteristic  also  of  the 
axones  (tracts  and  fasciculi)  of  many  neurone  groups  in  the  central  nervous  system. 

Owing  to  the  presence  of  these  migrating  cells  as  well  as  of  mesodermal  cells, 
the  peripheral  nerves  in  their  earlier  stages  appear  cellular  in  character;  later  the 
fibrous  elements  predominate,  the  nuclei  becoming  more  scattered  and  changing 
into  the  flatter  nuclei  characteristic  of  the  neurilemma  (Fig.  432).  According  to 
one  view  (Balfour),  the  nerve  fibers  themselves  are  differentiated  from  the  cyto- 


494  TEXT-BOOK  OF  EMBRYOLOGY. 

plasm  of  these  cell-strings  and  are  thus  multicellular  structures.  Still  another 
view  is  that  of  Hensen,  according  to  which  the  fibers  are  a  differentiation  in 
situ  from  preexisting  syncytial  bridges  uniting  the  parts  connected  subsequently 
by  the  formed  nerve  fibers.  This  differentiation  may  not  be  primarily  con- 
nected with  the  neuroblasts  (Apathy,  Paton) .  An  intermediate  view  between 
this  and  the  outgrowth  view  of  His  is  that  of  Held,  according  to  which  the 
neurofibrillar  substance  is  an  outgrowth  from  the  neuroblast  body,  or  at  least  a 
differentiation  proceeding  from  that  body,  but  always  within  the  preexisting 
cellular  bridges  of  Hensen.  The  differentiating  fiber  is  thus  always  intracel- 
lular  instead  of  intercellular  as  according  to  the  His-Cajal  view.  The  experi- 
ments of  Harrison  above  alluded  to,  in  which  the  accompanying  migrating  cells 
were  eliminated  and  naked  axones  (axis-cylinders)  nevertheless  developed,  ap- 
parently disposes  of  the  cell-string  theory  of  Balfour.  The  growth  of  the 
fibers  in  the  marginal  layer  of  the  central  nervous  system  is  also  unfavorable  to 
this  theory.  The  apparently  proven  capacity  of  growing  axones  to  find  their 
way  through  foreign  tissues  (aberrant  regenerating  nerve  fibers,  Cajal), 
through  ventricular  fluid  (Cajal),  and  even  through  serum  (Harrison)  seems  to 
throw  the  weight  of  evidence  in  favor  of  the  view  of  His.  The  latter  is  the 
view  adopted  in  this  description,  though  many  of  the  most  important  facts  of 
development  are  not  perhaps  entirely  irreconcilable  with  any  of  these  views. 
The  general  conception  of  the  neurone  is  affected  by  these  questions  and  the 
related  question  of  anastomoses  between  the  nervous  elements,  whether  present 
at  all,  and  if  present,  whether  primary  or  secondarily  acquired. 

From  the  above  it  would  seem  that  the  cells  of  the  neural  crest  have  the 
capacity  of  differentiating  into  afferent  neurones,  efferent  (sympathetic)  neurones 
and  supporting  cells.  Other  cells  of  the  jneural  crest  differentiate  into  the 
chromaffine  cells  of  the  suprarenal  glands  and  similar  structures  (p.  426). 

There  are  several  views  as  to  the  development  of  the  myelin  sheath.  Ac- 
cording to  one  view  (Vignal),  it  is  a  product  of  the  neurilemma  cells,  being 
formed  in  a  manner  analogous  to  the  formation  of  fat  by  fat  cells.  Accord- 
ing to  Wlassak,  the  various  substances  composing  the  myelin  (fat,  lecithin 
and  protagon)  are  first  found  in  the  central  nervous  system  in  the  protoplasm 
of  the  spongioblasts,  their  probable  original  source  being  the  blood  of  the 
meningeal  blood  vessels.  Later,  the  myelin  is  laid  down  around  the  axones, 
appearing  first  as  drops  or  granules.  The  same  process  takes  place  in  the 
peripheral  nervous  system.  The  supporting  elements  of  the  nervous  system 
thus  would  have  a  chemical  as  well  as  a  mechanical  function.  Another  view 
(Gurwitsch)  is  that  the  myelin  is  a  product  of  the  axone  and  is,  at  its  first 
appearance,  quite  distinct  from  the  neurilemma  cells. 

As  the  appearance  of  the  myelin  sheath  is  a  final  stage  in  the  development  of  the  neurone, 
the  various  neurone  systems  would  naturally  become  myelinated  in  about  the  same  sequence 


THE  NERVOUS  SYSTEM.  495 

in  which  their  axones  develop.  "  This  is  probably  true  in  a  general  way,  but  the  development 
of  both  axones  and  sheaths  requires  further  study  before  any  law  can  be  exactly  formulated. 
Coarse  fibers  apparently  become  medullated  early,  the  sheaths  of  such  fibers  being  usually 
thicker. 

Although  the  myelin  sheath  is  apparently  an  accessory  structure,  its  formation  is  of 
great  importance,  not  only  from  the  above  reason,  but  also  because  its  appearance  possibly 
indicates  the  assumption  by  the  neurone  of  its  capacity  for  the  precise  performance  of  its 
final  functions.  The  functional  significance  of  the  myelin  sheath  is  not,  however,  entirely 
clear.  Its  importance  is  enhanced  by  the  fact  that  its  integrity  depends  upon  the  integrity 
of  its  neurone  and  that  we  possess  precise  stains  for  demonstrating  both  its  normal  and 
abnormal  conditions. 

In  the  region  of  the  RHOMBENCEPHALOX,  the  neural  crest  very  early  exhibits 
a  division  into  three  masses:  a  glossopharyngeo-vago-accessorius,  an  acustico- 
facialis,  and  a  trigeminus.  These  masses  soon  become  separated  from  each 
other  and  from  the  neural  tube,  the  glossopharyngeus  also  shoeing  a  partial 
separation  from  the  vago-accessorius  mass  (Fig.  434). 

The  vago-accessorius  group,  at  about  three  weeks,  is  a  mass  of  cells  much 
larger  at  the  cranial  end  and  continuous  by  a  narrow  band  of  irregular  cells 
with  the  spinal  neural  crest.  The  cranial  end  of  the  mass  shows  a  partial 
division  into  a  dorsal  and  ventral  part.  The  former  becomes  the  ganglion  of 
the  vagus  root,  the  latter  the  ganglion  of  the  trunk  (nodosum).  The  glosso- 
pharyngeus  mass  likewise  shows  a  division  into  a  dorsal  group  of  cells,  the 
future  ganglion  of  the  root  and  a  ventral  group,  the  future  ganglion  of  the 
trunk  (petrosum).  The  two  ventral  groups  are  associated  with  epidermal 
thickenings  (placodes),  but  it  is  doubtful  whether  any  ganglion  cells  are 
derived  from  the  thickenings.  These  thickenings  probably  represent  the 
thickenings  associated  in  water-inhabiting  Vertebrates  with  the  development  of 
certain  sense  organs,  either  lateral  line  or  epibranchial  (see  p.  452).  At  this 
stage  there  are  no  afferent  fibers,  the  cells  not  yet  being  differentiated  into 
neurones.  Some  fibers  found  among  the  cells  are  efferent  (see  p.  488).  The 
glossopharyngeus  cells  lie  in  the  region  of  the  third  branchial  arch,  the  vagus 
in  the  region  of  the  fourth. 

During  the  fourth  and  fifth  weeks  the  processes  of  the  cells  begin  to  develop 
(Fig.  434),  and  the  cell  masses  finally  become  definite  ganglia  with  afferent  root 
fibers  passing  into  the  neural  tube  and  peripheral  processes  passing  outward, 
forming,  with  the  associated  efferent  fibers,  the  peripheral  branches  of  the  nerves 
in  question  (Fig.  435).  The  root  and  trunk  ganglia  of  the  vagus  and  glosso- 
pharyngeus, respectively,  are  also  now  connected  by  fiber  bundles  instead  of 
cellular  strands.  At  the  same  time  there  is  a  diminution  of  cells  in  the  caudal 
part  of  the  vago-accessorius  group,  this  part  finally  being  composed  almost  ex- 
clusively of  efferent  fibers  emerging  from  the  lateral  surface  of  the  medulla  and 
cord .  A  few  groups  of  cells  (accessory  root  ganglia)  persist,  however,  and  develop 


496 


TEXT-BOOK  OF  EMBRYOLOGY. 


into  ganglion  cells,  some  being  found  there  at  birth  (Streeter) .  This  would  in- 
dicate the  presence  of  a  small  and  hitherto  undetected  afferent  element  in  the 
spinal  accessory  nerve,  which  is  usually  regarded  as  purely  efferent.  The  spinal 
accessory  nerves  are  thus  identical  with  the  vagus  in  their  early  development 
and  consist  at  first  of  a  homologous  series  of  efferent  roots  and  ganglia.  This 


/x-x-x/  gang,  crest. 


Qpthal  dlv. 

Sup.  max  d 
N.maSticatorfus. 
Infmax.di 


D.I. 


FIG.  434. — From  a  reconstruction  of  the  peripheral  nerves  in  a  human  embryo  of 

4  weeks  (6.9  mm.).     Streeter. 

JII-XII,  III  to  XII  cranial  nerves;  C.I,  D.  I..,  L.I.,  5.7.,  ist  cervical,  ist  dorsal,  ist  lumbar,  and 
ist  sacral  nerves,  respectively;  I,  2,  3,  branchial  arches;  Ot.  v.,  auditory  vesicle;  IX-X-XI 
gang,  crest,  ganglionic  or  neural  crest  of  IX,  X  and  XI  cranial  nerves.  Fiber  masses  are 
represented  by  fine  lines,  ganglion  cell  masses  by  dots. 

indicates  that  the  spinal  accessory  might  be  regarded  as  a  specialized  part 
of  the  vagus  extending  caudally  into  the  cord  (Streeter)  (see  p.  464).* 

From  this  point  on,  the  further  development  of  the  efferent  fibers  of  the  X 
and  XI  nerves  and  of  the  peripheral  processes  of  their  ganglia  is  the  further 

*  According  to  another  view  (Bremer),  the  spinal  accessory  nuclei  and  roots  are  to  be  regarded  as 
representing  a  specialization  of  lateral  nuclei  of  the  ventral  gray  column  of  the  cord  whose  root  fibers 
pass  in  the  dorsal  branches  of  the  spinal  nerves  to  the  dorsal  trunk  musculature  (p.  487,  ccmp.  Fig. 
404) .  According  to  this  view,  the  muscles  innervated  by  the  XI  would  be  somatic.  The  possible 
homology  of  the  lateral  efferent  nuclei  and  roots  of  the  medulla  with  those  dorsal  root  fibers  of  the 
cord  which  arise  from  cells  in  the  ventral  gray  column  (p.  487  and  Fig.  430)  may  be  mentioned  in 
this  connection. 


THE  NERVOUS  SYSTEM. 


497 


growth  of  the  various  branches  of  these  nerves  and  their  connection  with  the 
differentiating  structures  innervated  by  them.  At  the  same  time  there  is  an  in- 
creasing concentration  of  the  cells,  thereby  forming  more  definite  ganglionic 


Vesicula  auditiva 


Gang,  acusticum 
Gang,  semilunare  n.V 


Gang.  radicisn.IX 
Gang,  petrosum 

Gang,  radicis  n.X 


N.  frontalis""" 


N.  mandibularis 
Gang,  geniculatum  --"' 
N.  chorda  tympani .---' 


ang.  Froriep 


•N.  hypoglossus 


ng.  nodos. 

-N.  desc.  cerv. 
"Rami  hyoid. 
(Ansa  hypoglossi) 

~N.  musculocutan. 
— N.  axillaris 
"N.  phrenicus 
-N.  medianus 

—X.  radialis 

— N.  ulnaris 

ITh. 


Tubus  digest.^' 


N.  femoralis 
N.  obturatorius 


R.  posterio 

R.  terminalis  lateralis 
R.  terminalis  anterior 
Mesonephros 
Nn.  ilioing.  et  hypogastr. 


FIG.  435.  —  Lateral  view  of  a  reconstruction  of  a  10  mm.  human  embryo,  showing  the  origin  and 
distribution  of  the  peripheral  nerves.  The  ganglionic  masses  are  represented  by  darker  and 
the  fiber  bundles  by  lighter  shading.  For  purposes  of  orientation  the  diaphragm  and  some 
of  the  viscera  are  shown.  The  arm  and  leg  are  represented  by  transparent  masses  into  the 
substance  of  which  the  nerve  branches  may  be  followed.  Streeter. 


498 


TEXT-BOOK  OF  EMBRYOLOGY. 


masses.  The  changes  taking  place  are  similar  to  those  exhibited  in  the 
differentiation  of  the  spinal  nerves  (p.  490).  The  central  relations  of  the 
nerves  of  this  region  of  the  medulla  are  shown  in  Fig.  436.  (Comp.  Fig.  407). 
The  glossopharyngeus  at  the  same  time  develops  its  branches,  most  of  the 
peripheral  fibers  running  in  the  third  arch  (lingual  branch).  Somewhat  later 
(12  to  14  mm.  embryo)  another  bundle  (tympanic  branch)  (Fig.  435)  passes  for- 
ward to  the  second  arch.  This  forms  the  typical  branchiomeric  arrangement 
in  which  there  is  a  forking  of  the  nerve  into  prebranchial  and  postbranchial 
branches,  the  latter  being  larger  and  containing  the  efferent  element  (see  p.  464 
and  Fig.  405). 


Roof  plate 

Alar  plate 
Fourth  ventricle 


Tractus  solitarius 

(in  marginal  layer) 


Efferent  nu.  N.  X. 
Nucleus  N.  XII.    - 

Ganglion  N.  X.     _J 


•     Sulcus  limitans 


-    Inner  layer     } 


"    Mantle  layer  } 


of  basal 
plate 


~  Ventro-lat.  column 
(in  marginal  layer) 

Floor  plate 


FIG.  436. — Transverse  section  through  the  rhombic  brain  of  a  10.2  mm.  human  embryo  (during  the 
fifth  week).     X,  Vagus;  XII,  Hypoglossus.     His. 

While  the  ganglia  of  the  facialis  and  acusticus  are  derived  from  the  same 
mass  of  cells  (p.  495,  Fig.  434)  and  are  later  still  in  very  close  apposition,  it  must 
be  remembered  that  they  are  totally  different  in  character.  At  four  weeks  they 
are  differentiated  from  each  other  (Fig.  437).  The  relations  of  the  two  ganglia 
are  shown  in  Figs.  435  and  437.  It  is  probable  that  the  ganglion  of  the  facial 
(geniculate  ganglion)  shows  an  early  differentiation  into  dorsal  and  ventral 
parts  similar  to  the  ganglia  of  the  IX,  and  X,  and  also  has  associated  placodes. 
The  peripheral  branches  of  the  cells  of  the  geniculate  ganglion  develop  into  the 
great  superficial  petrosal  and  chorda  tympani.  Both  of  these  nerves  enter  into 
secondary  relations  with  the  V.  There  is  some  doubt  as  to  whether  the  chorda 
is  a  prebranchial  or  postbranchial  nerve  (Fig.  435;  also  compare  p.  462  and 
Figs.  405  and  406). 


THE  NERVOUS  SYSTEM. 


499 


The  VII,  IX  and  X  are,  as  already  mentioned,  branchial  (splanchnic) 
nerves  and  the  central  processes  of  their  ganglia  all  have  a  common  destina- 
tion; they  grow  into  the  lateral  surface  of  the  medulla  oblongata,  enter  the 
marginal  layer  of  the  alar  plate,  and  there  bend  caudally,  forming  a  comrion 
descending  bundle  of  fibers  in  the  marginal  layer,  the  tractm  solita.-ius 
(Figs.  436  and  470;  see  also  pp.  462,  465). 

The  acoustic  ganglionic  mass  is  elongated  at  an  early  stage,  and  is  in  c  on- 
r.ection  with  an  ectodermal  thickening  (placode)  which  gives  rise  to  the  acoi  stic 


Roof  plate 


If"-  Alar  plate 


Sulcus  limitans 


Basal  plate 


Floor  plate 

FIG.  437. — Transverse  section  through  the  acoustic  region  of  the  rhombic  brain  of  a  10.2  mm.  human 
embryo.  VI,  Abducens  and  its  nucleus;  VII  G.  g.,  geniculate  ganglion;  77/7  G.  c.,  cochlear 
ganglion  of  acoustic  nerve;  VIIIG.v.,  vestibular  ganglion  of  VIII  nerve.  His. 

receptors  (p.  591).  From  the  upper  part  of  the  mass  a  bundle  of  peripheral 
processes  forms  a  branch  which  subsequently  innervates  the  ampullae  of  the 
superior  and  lateral  semicircular  canals  and  the  utricle,  while  from  the  lower 
part  a  branch  develops  to  the  ampulla  of  the  posterior  canal  and  to  the  saccule. 
The  nerve  and  ganglion  (ganglion  of  Scar  pa)  is  thus  at  first  vestibular  and  at 
this  stage  the  cochlear  part  of  the  ear  vesicle  is  not  indicated  as  a  separate  out- 
growth. As  the  lower  border  of  the  vesicle  grows  out  into  the  cochlea,  the 
lower  border  of  the  ganglion  becomes  thickened  and  develops  into  the  cochlear 
ganglion  (the  ganglion  spirale).  It  will  be  recalled  that  the  vestibular  part  of 


500 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  ear  is  the  older  part  phylogenetically,  the  cochlea  being  a  more  recent  special- 
ized diverticulum  of  the  older  structure.    (See  p.  592  and  Figs.  512  and  513.) 

The  central  processes  of  the  acoustic  ganglionic  mass  first  develop  from  the 
upper  part,  forming  the  vestibular  nerve  root  which  enters  the  marginal  layer  of 
the  medulla.  A  portion  at  least  of  its  fibers  bends  caudally,  forming  a  de- 
scending tract.  The  central  processes  of  the  cells  of  the  cochlear  ganglion, 
forming  the  cochlear  nerve  root,  pass  dorsally,  cross  the  vestibular  ganglion  and 
enter  the  medulla  dorsal  and  lateral  to  the  vestibular  root  fibers  (Fig.  437). 

Roof  plate 


FIG.  438. — Transverse  section  through  the  rhombic  brain  in  the  region  of  the  trigeminus  (V)  nerve 
of  a  10.2  mm.  human  embryo,  a.  W.,  Spinal  V;  G.G.,  Gasserian  ganglion;  V.m.,  efferent 
root  of  V  nerve.  His. 

The  trigeminus  is  the  most  anterior  of  the  ganglionic  masses  (Fig.  434). 
Embryological  evidence  has  been  brought  to  show  that  it  consists  of  two  or 
more  nerves  which  subsequently  fuse.  Placodes  have  also  been  described. 
It  is  possible  that  such  placodes  represent  those  belonging  to  the  most  anterior 
division  of  the  lateral  line  system  in  lower  forms,  and  probably  in  this  case 
would  not  properly  belong  to  the  V  (comp.  Fig.  405).  From  the  ganglionic 
mass  (Gasserian  or  semilunar  ganglion)  the  three  principal  branches — oph- 
thalmic, maxillary  and  mandibular — are  formed,  the  two  latter  passing  into  the 


THE  NERVOUS  SYSTEM. 


501 


Roof  plate 


Floor  plate 


FIG.  439. — Transverse  section  through  the  trigeminal  region  of  the  rhombic  brain  of  a  10.2  mrru 
human  embryo,  a.  W.,  Spinal  V;  V.  s.,  Gasserian  ganglion;  V.  m.,  part  of  efferent  root  of 
V  nerve.  His. 


FIG.  440.     Part  of  a  transverse  section  through  -the  rhombic  brain  of  a  chick  embryo  toward  the 

fourth  day,  showing  the  trigeminal  roots.     Cajal. 
A,  part  of  the  efferent  (masticator)  nucleus  of  the  V;  B,  efferent  root  of  the  V;  C,  bipolar  cells  of 

the  Gasserian  ganglion;  D,  beginning  of  descending  tract  (spinal  V)  formed  by  the  central 

processes  of  C. 


502  TEXT-BOOK  OF  EMBRYOLOGY. 

maxillary  process  and  mandibular  arch,  respectively  (Fig.  435).  The  central 
processes,  forming  the  afferent  root  (portio  major]  of  the  V,  enter  the  marginal 
layer  of  the  alar  plate  of  the  rhombencephalon  and  form  a  descending  bundle, 
the' spinal  V  (Figs.  438,  439,  440  and  470). 

The  trigeminus  exhibits  its  spinal-like  character  in  the  behavior  of  its 
visceral  portion  (comp.  p.  491).  Cells  of  the  ganglionic  mass  migrate  further 
peripherally  and  form  sympathetic  ganglia  (ciliary,  ode,  spheno palatine  (?) 
submaxillary(?)  ).  As  in  the  cord,  the  question  has  arisen  whether  efferent 
roots  may  not  also  contribute  a  portion.  Cells  have  been  described  as  migrat- 
ing with  the  oculomotor  root  fibers  and  forming  part  of  the  ciliary  ganglion 
(Carpenter). 

Besides  those  already  described  (cerebrospinal,  sympathetic),  the  only 
other  peripheral  neurones  of  the  nervous  system  are  connected  with  the  PROS- 
ENCEPHALON  and  are  a  part  of  the  eye  and  nose.  The  visual  receptors  (rods 
and  cones)  and  peripheral  afferent  neurones  (bipolar  cells)  appear  to  be  repre- 
sented by  portions  of  the  retina  and  are  described  elsewhere  (Chap.  XVIII). 

In  the  nose  there  is  first  a  placode  (p.  452)  from  which  neuroblasts  develop. 
Some  of  these  migrate  toward  the  neural  tube  and  probably  differentiate  into 
lemmocytes,  a  few  becoming  ganglion  cells.*  The  majority  of  the  neuroblasts 
remain  in  the  olfactory  epithelium,  sending  their  axones  (fila  olfactoria)  into 
the  olfactory  bulb,  the  peripheral  afferent  olfactory  neurones  thus  apparently 
displaying  the  primitive  ectodermal  location  of  afferent  peripheral  neurones 
(p.  448  and  Fig.  397).  (Comp.  p.  584.) 

Development  of  the  Lower  (Intersegmental)  Intermediate  Neurones. 

It  has  already  been  seen  how,  by  migration  and  by  differentiation  of  the  cells 
during  migration,  the  nucleated  layer  comprising  the  greater  part  of  the  thick- 
ness of  the  wall  of  the  neural  tube  is  differentiated  into  two  layers — an  inner 
nucleated  layer  retaining  its  earlier  characteristics,  and  an  outer  nucleated 
(mantle)  layer,  composed  largely  of  the  differentiating  neuroblasts  and 
characterized  in  ordinary  staining  by  more  widely  separated  nuclei.  It  has 
also  been  seen  that  this  differentiation  takes  place  earlier  and  more  rapidly  at 
first  in  the  ventral  part  of  the  lateral  walls  (basal  plate),  and  that  the  first  cells  to 
migrate  and  differentiate  are  those  whose  axones  grow  out  through  the  neural 
wall  and  pass  out  as  the  ventral  root  fibers. 

Not  much  later  than  the  above  differentiation  of  the  efferent  peripheral 
neurones,  axones  of  other  neuroblasts  also  grow  toward  the  periphery  of  the 
tube  but  do  not  pass  beyond  its  wall.  Such  neuroblasts  become  intermediate 

*  The  latter  are  probably  transient,  but  possibly  in  some  forms  persist  as  the  ganglion  cells  of  the 
Jiervus  terminalis  of  Pinkus. 


THE  NERVOUS  SYSTEM. 


503 


neurones  (p.  449).  The  migrating  bodies  of  these  neuroblasts  are  checked  at 
the  inner  boundary  of  the  marginal  layer,  but  their  growing  axones  enter  the 
marginal  layer  and  there,  apparently  on  account  of  their  inability  to  penetrate 
the  external  limiting  membrane,  turn  cranially  or  caudally,  or  bifurcate,  and 
form  longitudinal  ascending  and  descending  fibers.  These  longitudinal  fibers 
constitute  a  part  of  the  future  white  columns  (see  p.  507) ,  and  their  cells  are 
therefore  often  called  column  cells.  Many  axones  from  such  cells  in  all  parts 
of  the  lateral  walls  (Jteleromeric  or  commissural  column  cells)  pursue  a  ven- 
tral course  through  the  mantle  layer,  arching  around  near  the  periphery  and 


FIG.  441. — Part  of  a  section  through  the  lumbar  spinal  cord  of  a  76-hour  chick  embryo.     Cajal. 
A,  Ventral  root;  5,  spinal  ganglion;  C,  bifurcation  of  dorsal  root  fibers  forming  beginning  of  dorsal 
funiculus;  a,  b,  c,  neuroblasts  showing  various    stages  of  differentiation    into   intermediate 
neurones,  some,  at  least,  (c)  becoming  heteromeric  column  cells;  d,  efferent  neurone. 


crossing  the  floor  plate,  ventral  to  the  lumen,  to  become  longitudinal  ascending 
and  descending  fibers  in  the  marginal  zone  of  the  opposite  side.  These  early 
decussating  axones  form,  in  the  cord,  the  beginning  of  the  anterior  commissure 
(Fig.  441).  Other  neuroblasts,  the  axones  of  which  do  not  cross  the  median 
line,  become  tautomeric  column  cells. 

It  is  about  this  time  that  the  afferent  root  fibers  enter  the  marginal  layer  of 
the  dorsal  part  (alar  plate)  of  the  lateral  wall  and  form  in  the  marginal  layer 
the  various  bundles  of  longitudinal  fibers  above  described  (dorsal  funiculus, 
tractus  solitarius,  descending  vestibular,  and  spinal  V)  (Figs.  441,  442,  436,  437^ 


504  TEXT-BOOK  OF  EMBRYOLOGY. 

439,  440  and  470).  In  the  cord  the  ascending  arms  grow  to  a  greater  length 
than  the  descending.  In  the  rhombic  brain  the  reverse  is  usually  the  case. 

The  longitudinal  fibers  of  the  afferent  roots  and  of  the  intermediate  neurones 
thus  form  an  external  layer  occupying  the  marginal  layer  of  the  neural  tube. 
This  is  the  beginning  of  the  differentiation  into  white  and  gray  matter,  i.e., 
into  that  part  of  the  neural  tube  containing  only  the  axones  of  the  neurones 
and  into  that  part  containing  the  cell  bodies  and  the  beginnings  and  termina- 
tions of  the  axones.  The  terminations  of  axones  are  formed  by  a  turning  of 
the  longitudinal  fibers  into  the  mantle  layer  or  gray  matter  to  form  there 
terminal  arborizations.  Later,  the  longitudinal  fibers  develop  branches  (col- 
laterals) which  also  pass  into  the  gray  matter.  The  differentiation  of  the 
white  matter  is  completed  several  months  later  by  the  myelination  of  the 
nerve  fibers. 

The  longitudinal  axones  of  intermediate  neurones  which  are  formed  at  this 
period  in  the  cord  and  epichordal  brain  are  located  ventrally  near  the  median 
line.  These  medial  tracts  occupy  the  position  of  the  future  medial  longitu- 
dinal fasciculi,  the  reticulo-spinal  and  ventral  ground  bundles,  and  may  be 
regarded  on  both  comparative  anatomical  and  embryological  grounds  as  a 
primitive  system  of  long  and  short  ascending  and  descending  tracts  mediating 
between  cerebrospinal  afferent  and  efferent  peripheral  neurones,  and  not 
having  at  this  period  connections  with  the  higher  centers.  Other  more  lateral 
tracts  of  this  character  are  formed  somewhat  later,  the  whole  forming  the 
beginning  of  the  reticular  formation  +  ventro-lateral  ground  bundle  system 
(compare  Figs.  442,  449,  452  and  454). 

While  merging  more  or  less  imperceptibly  into  the  following  stages,  it  may 
in  a  general  way  be  said  that  at  this  stage  of  development  there  is  differentiated 
what  might  be  termed  the  primary  and  probably  the  oldest  coordinating  mech- 
anism of  the  nervous  system,  most  clearly  segmental  in  character  and  having 
general  features  common  not  only  to  all  Vertebrates,  but  to  many  Invertebrates. 
It  is  characterized  by  afferent  and  efferent  peripheral  neurones  arranged  seg- 
mentally  and  connected  longitudinally  in  the  central  nervous  system  by  crossed 
and  uncrossed  intersegmental  intermediate  neurones.  (Compare  pp.  465  and 
466) .  At  the  anterior  end  of  this  part  of  the  nervous  system  (epichordal  segmen- 
tal brain)  there  are  also  exhibited  differentiations  due  to  fundamental  vertebrate 
differentiations  in  the  peripheral  receptive  and  effective  apparatus.  Some  of 
these  are:  (i)  The  differentiation  of  the  splanchnic  (visceral)  receptive  and 
motor  apparatus,  giving  rise  in  the  nervous  system  to  (a)  a  separate  system  of 
afferent  root  fibers  (tractus  solitarius)  including  the  more  specialized  gustatory 
apparatus;  (b)  a  distinct  series  of  lateral  efferent  nuclei.  (2)  The  concentra- 
tion of  the  non-specialized  somatic  afferent  innervation  into  one  nerve  (tri- 


THE  NERVOUS  SYSTEM.  505 

geminus  and  its  central  continuation,  the  spinal  V).  (3)  The  specialized 
somatic  sense  organ,  the  ear,  with  its  older  vestibular  and  newer  cochlear 
divisions  with  central  continuations  of  its  nerves,  including  a  vestibular 
descending  tract. 

These  differentiations  of  the  peripheral  afferent  apparatus  lead  to  the  later 
formation  of  special  terminal  nuclei  for  their  central  continuations  and  second- 
ary tracts  from  these  nuclei  to  suprasegmental  structures  (p.  466,  Fig.  409). 

The  peripheral  and  intermediate  neurones  of  the  more  highly  modified 
cranial  end  of  the  tube,  or  FORE- BRAIN,  appear  to  lag  behind  in  development, 
but  in  its  basal  part  the  neuroblasts  are  beginning  to  be  differentiated  (fifth 
week).  In  the  development  of  the  eye,  the  brain  wall  is  evaginated,  carrying 
with  it  the  future  retina  comprising,  apparently,  the  sensory  epithelial  cells  or 
receptors  (rods  and  cones),  the  afferent  peripheral  neurones  (bipolar  cells  of 
retina)  and  the  receptive  or  primary  intermediate  neurones  (ganglion  cells  of 
retina  and  optic  nerve).  The  histogenesis  of  these  elements  is  dealt  with 
elsewhere,  but  it  may  be  pointed  out  here  that  the  axones  of  the  ganglion 
cells  of  the  retina  grow  toward  the  inner  side  of  the  optic  cup  (away  from 
the  original  luminal  surface),  pass  thence  in  the  marginal  layer  of  the  optic 
stalk,  undergo  a  partial  ventral  decussation  (optic  chiasma)  in  the  floor  plate, 
and  terminate  in  certain  thalamic  nuclei  (lateral  geniculate  bodies)  and  in  the 
roof  of  the  mid-brain.  The  so-called  optic  nerve  is  thus  obviously  a  central, 
secondary  tract.  The  development  of  this  tract  does  not  apparently  take  place 
until  a  later  period  than  the  differentiation  of  the  earlier  secondary  tracts  of  the 
cord  and  rhombic  brain  (after  the  sixth  week). 

In  the  case  of  the  olfactory  organ,  it  has  already  been  seen  that  the  peripheral 
neurones  develop  at  first  apart  from  the  neural  tube  and  send  their  axones 
into  the  olfactory  bulb.  The  latter  is  an  evagination  of  the  neural  tube 
which  receives  the  olfactory  fibers,  thereby  constituting  a  complicated  terminal 
nucleus  for  the  latter.  The  axones  of  bulb  cells  (the  mitral  cells}  which  pass 
along  the  stalk  of  the  bulb  are  thus  the  secondary  tract  of  this  system.  Many 
of  them  decussate  in  the  anterior  commissure.  Secondary  (and  tertiary) 
olfactory  tracts  find  their  way  to  caudal  parts  of  the  rhinencephalon  and  to 
hypothalamus,  thalamus  and  epithalamus,  forming,  with  other  tracts,  a  highly 
modified  prechordal  intersegmental  mechanism  (p.  537).  Other  olfactory  tracts 
proceed  to  the  suprasegmental  archipallium  which  develops  efferent  bundles 
to  the  segmental  brain. 

The  embryological  development  of  the  peripheral  apparatus,  especially 
of  its  receptive  portions,  as  shown  by  the  various  separate  ganglionic  rudiments 
(Fig.  434)  and  placodes,  exhibits  a  segmental  character  which,  though  not 
in  all  respects  primitive,  is  of  practical  value.  These  segments  are  (Adolf 
Meyer):  (i)  The  olfactory  apparatus,  nose,  without  efferent  elements.  (2) 


506  TEXT-BOOK  OF  EMBRYOLOGY. 

The  visual  apparatus,  eye,  with  the  eye-moving  III  and  IV  mid-brain  nerves 
as  its  efferent  portion.  (3)  The  general  sensory  apparatus  of  the  surfaces  of 
the  head  and  mouth,  the  afferent  trigeminus,  with  the  jaw-moving  efferent 
trigeminus.  (4)  The  auditory  (and  vestibular)  apparatus,  the  ear  (VIII 
nerve) ,  with  the  VI  (turning  the  eye  to  the  source  of  sound)  and  VII  (ear  and 
face  muscles)  efferent  nerves.  In  the  latter,  the  original  ear-moving  appa- 
ratus has  been  replaced  largely,  in  man,  by  the  muscles  of  expression.  (5) 
The  visceral  segment  (IX,  X,  and  XII  nerves),  not  indicated  externally  in 
forms  without  gills.  The  afferent  portion  is  concerned  with  taste  and  visceral 
stimuli,  the  efferent  with  tasting,  swallowing,  sound-production  and  other 
visceral  functions.  Overlapping  with  other  segments  is  due  to  its  visceral  as 
opposed  their  somatic  character.  The  apparent  dislocation  shown  by  the 
abducens  is  due  to  its  common  use  by  more  than  one  segment. 

Caudal  to  this  is  the  mechanism  for  head  movement  (N.  XI),  its  afferent 
portion  being  the  upper  spinal  nerves.  Following  this,  there  is  the  segmental 
series  of  spinal  nerves  which  in  places  shows  a  tendency  to  fuse  (plexuses)  into 
larger  segments  (phrenic  segment,  limb  segments) .  All  such  modifications  are 
expressions  of  more  recent  functional  adjustments  modifying  preexisting  ones. 

These  segments  may  be  regarded  as  a  series  of  reflex  arcs,  each  one  of 
which  may  have  a  certain  amount  of  physiological  independence  but  which 
are  associated  by  intersegmental  neurones.  The  latter  class  of  intermediate 
neurones  probably  effects  certain  groupings  of  various  efferent  neurones,  fur- 
nishing mechanisms  which  secure  harmonious  responses  of  groups  of  effectors 
involved  in  certain  definite  reactions  (e.g.,  limb-movements,  associated  eye 
movements).  These  effector-associating  mechanisms  may  be  acted  on  di- 
rectly (reflex)  by  afferent  neurones  or  by  the  efferent  arms  of  suprasegmental 
mechanisms. 

Superadded  to  this  segmental  apparatus  are  the  suprasegmental  mechan- 
isms which  develop  later,  the  pallium  being  the  last  to  be  completed.  These 
receive  bundles  from  the  segmental  nervous  system  and  send  descending 
bundles  to  the  intersegmental  neurones  (pp.  457,  465  and  466  and  Fig.  409). 

FURTHER  DIFFERENTIATION  OF  THE  NEURAL  TUBE. 
The  Spinal  Cord. 

From  this  time  on,  differences  of  structure  between  cord  and  epichordal 
segmental  brain  become  more  marked  and  make  it  more  convenient  to  treat 
their  later  development  separately.  The  ventral  half  of  the  cord  for  a  con- 
siderable period  maintains  its  lead  in  development.  At  four  weeks  (Fig.  442) 
this  lead  is  not  so  pronounced  as  in  the  immediately  following  period.  At 
this  stage  it  will  be  noticed  that  the  lumen  is  narrower  in  the  ventral  part, 


THE  NERVOUS  SYSTEM. 


507 


as  if  due  to  the  greater  thickening  of  the  ventral  walls  (basal  plates).  The 
increase  of  the  mantle  layer  (gray)  of  the  basal  plate  marks  the  beginning  of 
the  ventral  (anterior)  gray  column  or  horn.  The  increase  in  the  basal  plate 
may  be  partly  due  to  neuroblasts  migrating  from  the  alar  plate.  These 
would  be  intermediate  neurones.  The  development  of  the  mantle  layer  at 
the  expense  of  the  inner  layer,  due  to  differentiation  and  migration  of  the  cells 
of  the  latter,  is  well  shown,  but  is  more  marked  in  the  following  stages. 

As  already  mentioned,  the  axones  of  the  heteromeric  cells,  many  of  which 
lie  in  the  dorsal  half  of  the  lateral  walls,  after  decussating  (anterior  commis- 


Beginning  of 
dorsal  funiculu 

Dorsal  root 


Mantle  layer'' 


Ventral  root 

(from  neuroblasts 

of  mantle  layer) 


FIG.  442. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  4  weeks,  (6.9  mm.)  human  embryo. 
Dp,  Roof  plate;  Bp,  floor  plate.     His. 

sure),  form  longitudinal  fibers  in  the  marginal  layer  along  the  ventral  surface 
of  the  opposite  side,  mostly  mesial  to  the  emerging  ventral  roots  (Fig.  442). 
These  longitudinal  fibers  are  the  beginning  of  the  ventral  (anterior)  white  columns 
or  funiculi  of  the  cord.  The  sides  of  the  tube  between  the  dorsal  and  ventral 
roots  contain  at  first  only  a  few  longitudinal  fibers — the  beginning  of  the  ventro- 
lateral  funiculi.  Their  number  soon  rapidly  increases,  the  fibers  apparently 
coming  from  ventrally  located  tautomeric  cells.  The  dorsal  root  fibers,  as 
stated  before  (p.  490),  form  small  round  bundles  in  the  marginal  layer  of  the 
dorsal  halves  (Fig.  442).  This  is  the  beginning  of  the  dorsal  (posterior)  white 
columns  or  funiculi. 


508 


TEXT-BOOK  OF  EMBRYOLOGY. 


At  four  weeks  there  are  blood  vessels  in  the  mesodermal  tissue  surrounding 
the  neural  tube.  Branches  of  these  soon  penetrate  the  tube  itself. 

From  its  first  appearance  in  the  cord  as  an  oval  bundle,  during  the  fourth 
week,  the  dorsal  funiculus  steadily  increases  in  size,  forming  a  "root  zone"  in 
the  marginal  layer  of  the  dorsal  half,  but  not  reaching  the  roof  plate  (Fig.  443). 
This  increase  in  size  is  probably  produced  in  part  by  the  addition  on  its 
inner  side  of  overlapping  ascending  arms  of  dorsal  root  fibers  from  lower 


Partly  differentiated  mantle  layer 
Mantle  layer 


Dorsal  funiculus 
(post,  white  column) 


Dorsal  root 

Marginal  furrow 
Dorsal  spinal  artery/ 


Arcuate  fibers—- 


Cylinder furrow--; 


Lateral  gray^ 
column  (lat.  horn) 


Meningeal 
membrane 


Dp. 


Ventral  root ^ 


FIG.  443. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  4^  weeks  (10.9  mm.)  human  embryo.  His. 
A.s.,  Artery  in  ventral  longitudinal  sulcus;  A.sp.a.,  ventral  (anterior)  spinal  artery;  Bp,  floor  plate; 
Dp,  roof  plate;  7.  /.,  inner  layer.     The  faint  inner  outline  is  the  outline  of  the  cord  proper. 

cord  segments.  The  mantle  layer  of  this  part  contains  an  increasing  number 
of  cells  forming  curved  or  arcuate  fibers.  (Fig.  443.)  The  increase  in  the 
mantle  cells  of  the  dorsal  part  marks  the  beginning  of  the  dorsal  (posterior) 
gray  column  or  horn  (terminal  nucleus  of  the  dorsal  root  fibers).  Later,  other 
cells  become  differentiated  from  the  inner  layer  which  do  not  apparently  form 
arcuate  fibers  (Fig.  443)  and  which  subsequently  become  part  of  the  posterior 
horn.  It  is  possible  that  the  axones  of  some  of  these  cells  form  the  compara- 


THE  NERVOUS  SYSTEM. 


509 


tively  small  ground  bundles  of  the  dorsal  funiculus.  During  this  period 
of  development  of  the  dorsal  portions  of  the  lateral  walls  the  latter  have  ap- 
proached each  other,  reducing  the  dorsal  part  of  the  lumen  to  a  slit.  The 
roof  plate  has  undergone  a  slight  infolding  (Fig.  444).  Ventral  to  the  dorsal 
roots  there  is  a  groove  running  along  each  side  of  the  cord  (marginal  furrow  of 
His).  At  four  and  one-half  weeks  the  number  of  fibers  of  the  ventro-lateral 
funiculus  has  greatly  increased  and  another  groove  has  appeared  parallel  and 
ventral  to  the  marginal  furrow  and  forming  the  dorsal  boundary  of  the  ventro- 


Intermediate  plate 
Central  canal  • 


Floor  plate  -  - 


Vent.  long,  sulcus 


Dors,  funiculus 

Dors,  gray  column  (post,  horn) 

Dors,  root 
Marginal  furrow 
Cylinder  furrow 


Lat.  gray  column  (lat.  horn) 
Ventro-lat.  funiculus 

Vent,  gray  column  (ant.  horn) 
•  Vent,  root 


Vent,  funiculus 
(ant.  white  column) 


Vent.  sp.  artery 

FIG.  444. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  human  embryo 
of  18.5  mm.  (7^  weeks).     His. 

lateral  funiculus  (cylinder  furrow  of  His)  (Figs.  443  and  444).  The  portion 
of  the  lateral  wall  lying  between  these  two  grooves  or  furrows  forms  an 
intermediate  plate  which  contains  few  fibers  in  its  marginal  layer  at  this 
period,  and  is  thus  backward  in  development.  Grooves  appear  on  the  luminal 
wall,  apparently  corresponding  approximately  to  the  outer  grooves. 

The  further  growth  of  the  dorsal  funiculi  and  the  concomitant  growth 
of  the  associated  gray  matter,  i.e.,  of  the  cells  of  the  adjoining  mantle  layer, 
proceed  until  we  have  the  conditions  shown  in  Figs.  444  and  445.  At  the 
same  time  there  is  a  further  approximation  of  the  dorsal  portions  of  the  lateral 


510 


TEXT-BOOK  OF  EMBRYOLOGY. 


walls  so  that  the  widest  part  of  the  lumen  is  further  ventral.  At  about  eight 
weeks  the  portion  of  the  wall  near  the  median  line,  which  has  formed  a  ridge 
by  the  apposition  of  the  two  inner  layers  and  the  roof  plate  (Fig.  444  Y),  and  is 
uncovered  as  yet  with  fibers,  differentiates  a  marginal  layer  (eight  and  one-half 
weeks,  Fig.  445)  into  which  fibers  grow  forming,  on  each  side,  in  the  upper 
part  of  the  cord,  the  column  of  Goll  or  fasciculus  gracilis  (Fig.  446).  Many 
of  these  fibers,  at  least,  are  the  ascending  arms  of  caudal  dorsal  root  fibers, 
which  are  thus  added  mesially  to  the  continuations  of  upper  cord  roots.  It  will 


Rudiment  of  funiculus  gracilis 


Dorsal  funiculus  (cuneatus) 


Intermediate  plate 


Central  canal  • 

Floor  plate  - 
Vent.  long,  sulcus  —  - 


Dors,  gray  column 

-  -.  Dors,  root 

Marginal  furrow 
Cylinder  furrow 

Lat.  gray  column 

Ventro-lat.  funiculus 

Vent,  gray  column 

Vent,  root 
Vent,  funiculus 


Vent.  sp.  art. 

FIG.  445.  —  Half  of  a  transverse  section  of  the  spinal  cord  of  a  human  embryo  of 
24  mm.  (8|  weeks).     His. 

be  noted  that  there  is  now  a  massive  dorsal  gray  column  and  that  the  original 
oval  bundle  has  extended  around  on  the  mesial  side  of  this  gray  column. 

While  these  changes  are  taking  place,  the  dorsal  portions  of  the  lateral  walls 
have  fused,  probably  beginning  at  the  most  dorsal  part,  thus  forming  the  dorsal 
septum.  This  may  be  accompanied  by  a  certain  amount  of  rolling  in  from  the 
dorsal  part  indicated  by  the  direction  of  the  ependyma  cells  (Fig.  445)  .  The 
growth  of  the  ventral  funiculi  and  gray  columns  results  in  the  appearance 
and  subsequent  increasing  depth  of  the  ventral  longitudinal  fissure.  The  cord 
now  resembles  the  adult  cord  in  many  features,  having  well-marked  white*  and 

*The  term  "white  "  column  is  used  for  convenience.  The  funiculi  do  not  become  "white"  until 
their  fibers  become  myelinated  during  the  sixth  month. 


THE  NERVOUS  SYSTEM. 


511 


gray  columns,  but  contains  a  disproportionately  small  amount  of  fibers.  A 
further  and  later  change  consists  in  a  rolling  inward,  as  it  were,  of  the  dorsal 
gray  column  so  that  it  becomes  separated  from  the  ventral  gray  column,  and 
that  portion  of  it  formerly  facing  dorsally  comes  to  face  more  mesially,  the  roots 
entering  more  dorsally.  This  change  may  be  due  partly  to  the  development 
of  the  intermediate  plate  which  has  in  the  meantime  taken  place.  In  this 
plate  axones  of  tautomeric  cells  have  begun  to  form  the  limiting  layer  of  the 
lateral  funiculus.  From  the  cells  of  the  intermediate  plate  are  formed  the 
neck  of  the  dorsal  gray  column,  also  the  cells  of  Clarke's  column  and  the 

Funiculus  gracilis 


Dors,  funiculus  (cuneatus) 
Dors,  gray  column 
Dors,  root 

Marginal  furrow 

-\ Intermed.  plate 

—  Cylinder  furrow 

•!\"|~  ~"  Lat.  gray  column 

-  -  -  Ventro-lat.  funiculus 
Vent,  gray  column 

-  Vent,  root 

Vent,  funiculus 
Vent.  sp.  artery 
FIG.  446. — Half  of  a  transverse  section  of  the  spinal  cord  of  a  human  foetus  of  about  3  months.    His. 

processus  reticularis.  In  the  course  of  these  developments,  the  ventro-lateral 
ground  bundles,  formed  primarily  by  heteromeric  and  tautomeric  cord  cells, 
receives  various  accessions.  These  are  first  the  long  descending  inter- 
segmental  tracts  from  epichordal  brain  nuclei  in  the  formatio  reticularis 
which  as  they  proceed  down  the  cord  naturally  overlap  externally  the  ground 
bundles  already  formed  there.  They  include  the  medial  longitudinal  jasciculi, 
tracts  from  Deiters1  nuclei  and  the  rubro-spinal  tracts  which  occupy  the  ventro- 
lateral  funiculi  external  to  the  ground  bundles.  In  the  lateral  funiculi  there 
are  also  added  the  ascending  tracts  from  cord  nuclei  to  suprasegmental  structures. 


;*W '  ••;  .'.<-    S>-  ..•  .'  :  C'*."  5~.- 


512  TEXT-BOOK  OF  EMBRYOLOGY. 

These  are  the  dorsal  spino-cerebellar  tracts  from  Clarke's  columns,  ventral  spino- 
cerebellar  tracts,  and  tracts  to  mid-brain  roof  and  thalamus  (spino-tectal  and 
thalamic).  Finally  (fifth  month)  the  descending  tracts  from  the  pallium  are 
added,  the  direct  and  crossed  cortico- spinal  (pallio-spinal  or  pyramidal]  tracts, 
the  latter  being  thrust,  as  it  were,  into  the  lateral  funiculus. 

The  development  of  the  cord,  then,  is  produced  by  (i)  the  proliferation  of 
the  .epithelial  cells  and  the  formation  of  the  nuclear  and  marginal  layers ;  (2) 
the  multiplication,  differentiation  and  growth  of  the  neuroblasts  (mantle  layer) ; 
(3)  the  development  of  the  ventral  roots;  (4)  formation  of  the  funiculi  (white 
columns  when  myelinated)  by  the  growth  into  the  marginal  layer  of  (a)  dorsal 
root  fibers  of  the  cord,  the  ascending  arms  of  which  overlap  those  root  fibres 
entering  higher  cord  segments,  (b)  cord  neuroblasts  forming  intersegmental 
(ground  bundle)  tracts  next  to  the  gray  matter,  (c)  descending  intersegmental 
tracts  from  the  segmental  brain,  representing  continuations  principally  of  cere- 
bellar  efferent  tracts,  (d)  afferent  suprasegmental  tracts  from  cord  nuclei, 
(e)  descending  pallio-spinal  tracts.  In  addition  to  this,  there  are  general 
factors  of  growth,  such  as  increasing  vascularization,  increasing  amount  of 
neurone  cytoplasm  (especially  dendrites) ,  increased  size  of  axones  and,  finally, 
the  acquisition  by  the  latter  of  myelin  sheaths. 

The  vertebral  column  grows  faster  in  length  than  the  inclosed  spinal  cord. 
The  result  of  this  is  that  the  caudal  spinal  nerves  making  their  exit  through  the 
intervertebral  foramina  are,  so  to  speak,  dragged  caudalward  and  instead  of 
proceeding  outward  at  right  angle  to  the  cord,  pass  caudally  to  reach  their 
foramina.  The  leash  of  nerve  roots  thus  formed,  lying  within  the  caudal  part 
of  the  vertebral  column,  constitutes  the  cauda  equina.  The  coverings  of  the 
cord  retain  their  original  connections  at  the  caudal  end  of  the  vertebral  canal 
and  form  a  prolongation  of  the  cord  membranes  enclosing  the  thin,  terminal 
part  of  the  cord,  the  filum  terminate. 

The  Epichordal  Segmental  Brain. 

In  the  fifth  week,  the  walls  of  the  rhombencephalon  are  comparatively  thin. 
In  the  caudal  region  of  the  medulla  oblongata  (p.  477),  the  dorsal  part  of  each 
lateral  wall  is  upright  and  is  bent  at  a  considerable  angle  with  the  ventral 
part  (basal  plate),  the  groove  on  the  inner  surface  between  the  two  being  the 
sulcus  limitans.  The  roof  of  this  region  is  formed  by  the  thin  expanded  roof 
plate  (Figs.  436-439)- 

Anterior  to  this,  the  roof  plate  is  not  expanded,  the  alar  plates  almost 
meeting  in  the  mid-dorsal  line.  This  thicker  part  of  the  roof  is  the  rudiment 
of  the  cerebellum.  Its  caudal  edges  are  attached  to  the  expanded  roof  plate  (see 
P-  525). 


THE  NERVOUS  SYSTEM.  513 

In  front  of  the  cerebellum  the  tube  is  narrower  and  is  compressed  laterally. 
This  part  is  the  isthmus  (Fig.  447).  Anterior  to  this,  the  roof  plate  and  alar 
plates  expand  into  the  mid-brain  roof,  the  basal  and  floor  plates  forming  the 
basal  part  of  the  mid-brain. 

Certain  gross  changes  which  from  now  on  take  place  in  the  medulla  riay 
conveniently  be  noted  here.  At  about  this  time  (fifth  week)  the  outer  borders 
of  the  alar  plate  become  folded  outward  and  then  downward,  being  thus  turned 
back  on  the  plate  itself  (Figs.  452  and  416).  This  fold  is  called  the  prhwry 
rhombic  lip,  and  is  most  marked  along  the  caudal  border  of  the  cerebellum. 
The  folds  of  the  lip  then  fuse,  forming  a  rounded  eminence  composing  the  border 
of  the  alar  plate  to  which  the  roof  plate  is  attached  laterally.  Subsequently, 
the  attachment  to  the  roof  plate  is  shifted  dorsally  in  the  medulla,  caudally  in 


D.IV 


— Nu.  IV. 


FIG.  447. — Transverse  section  through  the  isthmus  of  a  10.2  mm.  human  embryo.     D.IV,  Decussa- 
tion  of  trochlear  nerve;  M.  /.,  marginal  layer;  Nu.  IV,  nucleus  trochlear  nerve.     His. 

the  cerebellum.  The  portion  of  this  lip  which  thins  off  into  the  roof  plate  is  the 
tcenia  of  the  medulla  and  the  posterior  velum  and  taenia  of  the  cerebellum.  The 
thin  roof  plate  itself  becomes  tbe  epithelial  part  of  the  tela  chorioidea  of  the 
fourth  ventricle.  At  the  caudal  apex  of  the  fourth  ventricle  a  fusion  of  the 
lips  of  the  opposite  sides  forms  the  obeoc. 

A  further  complication  is  due  to  the  increasing  pontine  flexure  by  which  the 
dorsal  walls  of  the  tube  are  brought  close  together  (Fig.  448).  The  transverse 
fold  of  the  tela  thus  produced  is  the  chorioid  fold.  At  about  the  same  time 
lateral  pocketings  outward  of  the  dorsal  wralls  occur  just  caudal  to  the  cere- 
bellum which  contain  portions  of  the  chorioid  fold.  These  are  the  lateral 
recesses.  By  further  growth  and  vascularization,  the  mesodermal  part  of  the 
chorioid  fold  forms  the  chorioid  plexus  of  the  fourth  ventricle  (metaplexus). 
Finally,  in  the  human  brain  an  aperture  appears  in  the  caudal  portion  of 
the  roof  of  the  ventricle — the  foramen  of  Magendie  (metapore) ;  and,  according 
to  many  authorities,  one  also  occurs  in  the  roof  of  each  of  the  lateral  recesses 


514 


TEXT-BOOK  OF  EMBRYOLOGY. 


— the  foramina  of  Luschka.  The  roof  of  the  fourth  ventricle,  where  present, 
is  thus  composed  of  an  inner  ependymal  epithelium — the  expanded  roof  plate 
of  the  neural  tube — and  an  outer  mesodermal  covering  containing  blood  vessels. 
Other  gross  changes  chiefly  involve  the  basal  plate.  At  the  beginning  of  the 
fifth  week  this  does  not  much  exceed  the  alar  plate  in  thickness  and  is  separated 
from  the  opposite  basal  plate  by  an  inner  median  sulcus  (Fig.  452).  The  basal 
plate  now  increases  in  thickness  and  thereby  both  deepens  the  sulcus  and  con- 
tributes to  a  flattening  out  of  the  lateral  walls,  so  that  all  portions  by  the  sixth 
week  lie  approximately  in  the  same  horizontal  plane  (Fig.  454).  Later,  the 
floor  plate  increases  in  thickness  more  rapidly  and  the  sulcus  becomes  shallower 
(eight  weeks)  (Fig.  455).  The  band  of  vertical  ependyma  fibers  passing  through 


Mesencephaion 


Epiphysis 
Diencephalon 


Isthmus 

Cerebellum 
Transverse  fold 
-  -Rhombic  lip 


Olfactory  lobe 
Optic  stalk 


Infundibulum         Hypophysis 
FIG.  448. — Lateral  view  of  a  model  of  the  brain  of  a 


, 

Basilar  artery 

weeks'  (18.5  mm.)  human  embryo.    His. 


it  is  the  septum  medulla.  It  is  bounded  on  each  side  by  a  vertical  extension  of 
the  marginal  layer  which  for  convenience  will  be  referred  to  as  the  septal 
marginal  layer  (Figs.  453,  454  and  455). 

The  histological  condition  of  this  part  of  the  tube  at  the  beginning  of  five 
weeks  has  already  been  described.  The  lateral  walls  consist  of  an  inner  layer 
of  closely  packed  cells,  of  a  mantle  layer  consisting  of  efferent  neurones  and  a 
simple  system  of  intermediate  neurones,  and  an  outer  marginal  layer  containing 
the  longitudinal  bundles  of  incoming  afferent  roots  and  longitudinal  axones  of 
intermediate  neurones  (see  p.  504).  It  has  been  seen  that  this  condition  has 
been  brought  about  by  the  proliferation  of  cells  near  the  tube  cavity,  which 
migrate  outward,  at  the  same  time  many  of  them  differentiating  into  neuro- 
blasts  and  nerve  cells  and  thereby  forming  the  mantle  layer.  As  in  the  cord, 
the  basal  plate  takes  the  lead  and  thus  at  first  outstrips  the  alar  plate,  as  shown 


THE  NERVOUS  SYSTEM.  515 

in  its  greater  thickness  above  mentioned.  This  process  likewise  terminates 
sooner  in  the  basal  plate,  few  cell  divisions  being  present  there  at  seven  weeks. 
At  about  the  end  of  the  fifth  week  (see  p.  519)  the  alar  plate  begins  to  develop 
very  rapidly.  Its  period  of  proliferation  is  about  terminated  at  the  end  of  the 
second  month.  When  the  cell  proliferation  near  the  ventricle  has  ceased, 
the  inner  layer  is  reduced  by  outward  migration  to  a  single  layer  of  epend]  ma 
cells  (compare  pp.  485  and  486). 

While  the  efferent  nuclei  continue  to  develop  and  the  central  continuations 
of  the  afferent  neurones  continue  to  grow  in  length,  the  principal  differential  ions 
now  taking  place  in  the  rhombic  brain  are  those  affecting  the  intermediate 
neurone  systems. 

The  first  of  these  to  be  considered  is  the  further  differentiation  of  the  system 
of  intersegmental  neurones  (p.  465).  The  earlier  development  of  this  system 
has  been  seen  to  involve  especially  the  basal  plate  and  the  further  development 
of  the  latter  leads  to  the  complete  differentiation  of  the  formatio  reticularis 
which  especially  represents  this  system  in  the  epichordal  brain.  It  has  already 
been  seen  (p.  504)  that  many  of  the  intermediate  neurones  representing  the 
beginning  of  this  system  seem  to  be  at  first:Jieteromeric  and  form  an  internal 
arcuate  system  of  fibers  similar  to  those  seen  in  the  cord  (pp.  503,  507).  They 
increase  in  number  toward  the  median  line  and  are  especially  numerous  in  the 
basal  plate,  where  they,  together  with  the  medial  efferent  neurones  (XII  and 
VI  cranial  nerves) ,  form  an  eminence  of  the  mantle  layer  corresponding  to  the 
ventral  gray  column  of  the  cord  (Fig.  449) .  Many  of  the  axones  of  these  cells 
of  the  arcuate  system  cross  the  septum  medullae,  thus  marking  the  beginning  of 
the  raphe,  and  form  on  each  side  a  longitudinal  bundle  in  the  septal  marginal 
layer  (Fig.  449).  These  longitudinal  bundles  correspond  to  the  first  formation 
of  the  ventral  funiculi  of  the  cord.  They  must  not,  of  course,  be  confused 
with  the  pyramids  which  appear  much  later.  Whether  these  longitudinal 
bundles  are  also  partly  formed  of  axones  of  tautomeric  cells  is  uncertain. 
Later,  as  the  anterior  horn  swellings  grow  and  the  depth  of  the  septum 
medullae  and  of  the  septal  marginal  layers  increases  (compare  p.  514),  more 
longitudinal  fibers  appear  in  the  latter,  the  new  ones  apparently  being  added 
ventrally.  Others  also  appear  more  laterally  in  the  marginal  layer  (Figs.  453, 
454  and  455).  (Compare  cord,  p.  507.)  At  this  time,  also,  fibers  enter  the 
marginal  layer  bordering  the  surface  (as  distinguished  from  the  septal),  pass 
along  parallel  with  the  surface,  cross  the  septum,  and  proceed  to  various  parts 
of  the  marginal  layer  of  the  opposite  side.  These  fibers  are  the  first  external 
arcuate  fibers  as  opposed  to  the  preceding  internal  arcuate  fibers  which  traverse 
the  mantle  layer  (gray)  in  the  arcuate  part  of  their  course  (Fig.  453). 

The  majority  of  the  longitudinal  fibers  entering  the  septal  marginal  layers 
during  the  second  month  occupy  approximately  the  position  of  the  future 


516 


TEXT-BOOK  OF  EMBRYOLOGY. 


mesial  formatio  reticularis  alba  (white  reticular  formation)  and  correspond  in 
position  to  the  fibers  of  the  medial  longitudinal  fasciculi  and  reticulo- spinal 
tracts  in  the  adult  medulla,  representing  probably  the  same  system  as  the 
medial  part  of  the  ventro-lateral  funiculi  of  the  cord  (medial  longitudinal 
fasciculi,  reticulo-spinal  and  ventro-medial  ground  bundles  of  the  cord) .  The 
medial  longitudinal  fasciculi  are  in  part  descending  fibers  from  higher  levels 
described  later. 

Taenia 

Marginal  layer 
Mantle  layer 


Alar  plate 


Sulcus  limitans 


Basal  plate 


Inner  la 


Tractus  solitarius 


N.  X. 
(Medullary  XI) 

Internal  arcuate  fibers 

(in  beginning  gray 

reticular  formation) 


N.  XII 


Ventral  funiculus  Floor  plate 

(beginning  of  form,  retic.  alba) 

FIG.  449. — Half  of  a  transverse  section  of  the  medulla  of  a  10.2  mm.  human  embryo.     His. 

In  the  basal  plate,  between  the  medial  and  lateral  efferent  nuclei,  there  are, 
even  at  the  beginning  of  the  fifth  week,  not  only  the  efferent  neurones  and  the 
heteromeric  (commissural)  neurones  already  mentioned,  but  other  neuroblasts 
whose  axones  have  a  radial  direction,  i.e.,  toward  the  periphery.  (Figs.  449 
and  452.)  The  interlacing  of  these  with  the  arcuate  fibers  forms  the  first 
indication  of  the  formatio  reticularis  grisea  (gray  reticular  formation) .  Later, 
longitudinal  fibers  are  present  here,  giving  rise  to  a  condition  more  fully 
corresponding  to  that  in  the  adult,  analogous  also  to  the  condition  in  the 
lateral  funiculi  of  the  cord,  especially  in  the  processus  reticularis. 


THE  NERVOUS  SYSTEM. 


517 


In  the  region  of  the  auditory  segment  an  important  neurone  group  appears 
which  is  possibly  a  differentiation  of  the  extreme  dorso-lateral  portion  of  the 
basal  plate.  This  is  Deiters^  nucleus,  which  apparently  receives  vestibu'ar 
and  cerebellar  fibers  and  sends  uncrossed  descending  bundles  along  the  outer 
later?,!  part  of  the  reticular  formation  and  also  ascending  and  descending  crossed 
and  uncrossed  fibers  along  its  outer  mesial  portion  (part  of  the  medial  Icngi- 
tudiial  fasciculus).  This  nucleus  thus  represents,  apparently,  like  the  nucleus 
rubar  and  nucleus  of  Darkschewitsch  (below),  a  differentiated  portion  of  the 
int  ;rsegmental  neurones  in  especial  connection  with  suprasegmental  efferent 
fibers  which  thereby  act  on  many  brain  and  cord  segments. 

The  great  development  of  the  reticular  formation  here  and  caudally  possibly 
causes  a  ventro-lateral  displacement  of  the  contained  nucleus  ambiguus  and 
efferent  facial  nucleus  and  consequently  the  arched  or  hook-shaped  course  of 


Germ  facialis 


medsulcus 


B 


medsiilcus 


FIG.  450. — Diagram  illustrating  the  development  of  the  genu  of  the  facial  nerve  in  the  human 
embryo.  The  drawings  show  the  right  facial  nerve  and  its  nucleus  of  origin,  in  three  stages: 
the  youngest,  A,  being  a  10  mm.  embryo,  and  the  oldest,  C,  a  new-born  child.  The  relative 
position  of  the  abducens  (VI)  nerve  is  represented  in  outline;  its  nerve  trunk  is  not  shown,  as 
the  structures  represented  are  seen  from  above.  Streeter. 

their  root  fibers  as  seen  in  transverse  section  (Streeter) .  At  the  same  time,  the 
nucleus  of  the  VI,  which  originally  was  caudal  to  the  VII,  migrates  cranially, 
carrying  the  facial  efferent  roots  with  it.  This  gives  rise  to  the  genu  facialis 
(Streeter,  Fig.  450). 

In  the  mid-brain  (Fig.  451),  what  appears  to  represent  the  basal  plate 
forms  an  eminence,  the  tegmental  swelling.  Later  there  is  differentiated  from 
this  the  reticular  formation  of  this  region,  containing  various  nuclei  and 
traversed  by  radial,  longitudinal  and  arcuate  fibers,  many  of  the  latter  arising 
from  the  later  differentiating  dorsal  portions  (corpora  quadrigemina)  of  the 
lateral  mid-brain  walls.  An  important  neurone  group  of  the  reticular  forma- 
tion system  which  appears  in  this  region  is  the  nucleus  of  Darkschewitsch.  Its 
descending  axones  form  a  part  of  the  medial  longitudinal  fasciculus  and 
probably  appear  at  the  end  of  the  first  month.  The  nucleus  ruber  is  probably 
differentiated  from  the  forward  extremity  of  the  tegmental  swelling  which  over- 
laps into  a  prechordal  region  (Fig.  463).  Its  axones  (crossing  asForersdecus- 
sation  and  forming  the  rubro-spinal  tract)  probably  develop  early.  This 


518 


TEXT-BOOK  OF  EMBRYOLOGY. 


neurone  group  apparently  owes  its  great  development  principally  to  its  close 
association  with  the  cerebellum.  These  two  long  descending  intersegmental 
tracts  as  they  grow  downward  envelop  the  differentiating  reticular  formation 
of  more  caudal  regions  of  brain  (and  cord)  and  thereby  come  to  occupy  an 
external  position  in  the  fully  differentiated  reticular  formation. 

The  reticular  formation  is  thus  composed  of  a  gray  portion  containing  the 
neurone  bodies  and  shorter  tracts  and  a  white  portion  composed  of  the  longer 
tracts.  Axones  from  certain  nuclei  (especially  N.  ruber,  N.  of  Darkschewitsch 
and  N.  of  Deiters)  form  long,  principally  descending,  tracts  which  envelop  the 
gray  reticular  formation  mesially  (medial  longitudinal  fasciculus  including 
fibers  from  nuclei  of  Darkschewitsch  and  Deiters  as  well  as  other  reticulo- 
spinal  fibers)  and  laterally  (rubro-spinal,  lateral  uncrossed  tract  from  Deiters' 


-••Alar  plate 


<^p*|  £'.«"'.,'*;•" — Marginal  layer 

>   ^%       "^ =•.-   •-  ^-C^^l 

x  %k~  «-viiKi^--NucIeusN-m 

I Root^N.m 


FIG.  451. — Transverse  section  through  the  mid-brain  of  a  10.2  mm.  human  embryo.     His. 

nucleus  and  other  reticulo-spinal  fibers)  and  constitute  the  white  reticular 
formation.  These  long  tracts  descend  to  the  cord  and  there  similarly  envelop 
its  ventro-lateral  ground  bundles. 

While  the  above  differentiation  of  the  reticular  formation  has  been  taking 
place,  changes  in  the  alar  plate  have  begun  which  lead  to  the  formation  of 
terminal  nuclei  of  peripheral  afferent  nerves,  as  well  as  terminal  nuclei  of  other 
tracts,  all  of  which  send  fiber  bundles  to  suprasegmental  structures. 

The  formation  of  the  receptive  nuclei  of  the  afferent  nerves  of  peripheral 
(segmental)  structures  is  complicated  by  the  fact  that  the  central  continuations 
of  the  peripheral  afferent  nerves  are  not  confined  to  their  own  respective  seg- 
ments but  form  longitudinal  tracts  which  continue  to  grow  upward  (columns  of 
Goll  and  Burdach)  or  downward  (descending  solitary,  vestibular  and  trigeminal 
tracts)  passing  into  other  segments  and  overlapping  externally  structures 
already  in  process  of  formation  there.  In  each  segment,  then,  the  terminal 
nuclei  of  the  afferent  nerves  of  that  segment  must  be  distinguished  from  the 


THE  NERVOUS  SYSTEM.  519 

terminal  nuclei  of  afferent  elements  from  other  segments.  The  latter  are 
external  or  added  to  the  former  and  are  differentiated  from  additional  prolifer- 
ations of  neuroblasts  of  the  alar  plate.  In  addition  to  these  nuclei,  there  are 
certain  nuclei  forming  links  between  the  two  great  suprasegmental  structures, 
the  pallium  and  cerebellum.  These  nuclei  are  the  olive*  and  pons  nuclei, 
both  of  which  form  afferent  cerebellar  bundles  and  which  are  differentiatec  by 
still  further  proliferations  and  migrations  of  alar  plate  neuroblasts. 

It  has  already  been  seen  that  the  afferent  peripheral  nerves  (IX  and  X) 
c-f  the  visceral  segment  form  (together  with  descending  fibers  of  the  VII)  the 
tractus  solitarius.  This  is  at  first  (5th  week)  short,  but  in  six  weeks  has  rea«  :hed 
the  cord.  The  terminal  nucleus  of  the  tractus  solitarius  is  differentiated  irom 
the  neuroblasts  of  the  medial  portion  of  the  alar  plate.  The  course  of  the 
axones  of  this  nucleus  is  not  known.  Judging  from  comparative  anatomical 
grounds,  they  would  not  follow  the  fillet  pathway  (C.  J.  Herrick).  The  most 
caudal  part  of  this  nucleus  is  the  nucleus  commissuralis  at  the  lower  apex  of  the 
fourth  ventricle. 

The  formation  of  the  other  terminal  nuclei  lying  in  the  region  of  this  seg- 
ment is  begun  by  the  further  developments  of  the  alar  plate  already  alluded 
to.  These  are  initiated  by  an  expansion  and  consequent  folding  of  its  border 
(formation  of  the  rhombic  lip,  p.  513),  followed  by  further  cell-proliferation, 
leading  to  fusion  of  these  folds  and  copious  formation  of  neuroblasts  in  this 
region.  These  neuroblasts  represent  fresh  accessions  to  the  neuroblasts 
already  formed  in  the  mantle  layer  of  the  more  medial  part  of  the  alar  plate. 
This  latest  development  of  the  border  portions  of  the  alar  plate  is  the  last  step 
in  the  progressive  development  of  the  neural  tube  from  the  medial  portion 
(basal  plate)  to  the  lateral  (dorsal)  border  of  the  lateral  walls  of  the  tube 
where  further  development  ceases  at  the  attachment  to  the  roof  plate  (teenia). 
(Fig.  452-) 

Many  of  the  neuroblasts  of  the  rhombic  lip  region  migrate  ventrally.t 
Some  of  those  from  the  medial  part  of  the  swelling  produced  by  the  fusion  of 
the  rhombic  lip  folds  (p.  513)  migrate  along  the  inner  side  of  the  tractus  soli- 
tarius, while  those  from  the  lateral  part  of  the  swelling  pass  outside  the  tractus, 
which  becomes  thereby  enclosed  in  the  mantle  layer  (Fig.  453).  Many  of  these 
neuroblasts  continue  their  journey,  passing  along  the  outer  side  of  the  differ- 


*  This  is  conjectural.  The  origin  of  fibers  to  the  inferior  olivary  nuclei  is  not  known.  The 
most  conspicuous  tract  to  the  olive  is  von  Bechterew's  central  tegmental  tract.  Purely  a  priori  con- 
siderations might  be  adduced  in  favor  of  this  being  considered  a  descending  tract  from  thalamic 
nuclei  which  in  turn  receive  pallio-thalamic  fibers.  It  may,  however,  arise  from  lower  optic  centers. 

fit  is,  perhaps,  an  open  'question  whether  the  formation  of  the  lip  is  a  fundamental  feature  in 
this  last  proliferation  and  invasion  of  neuroblasts  from  the  border  of  the  alar  plate.  The  promi- 
nence of  the  rhombic  lip  in  man  is  the  early  embryological  expression  of  the  future  great  develop- 
ment of  parts  subsequently  formed  from  this  portion  of  the  neural  wall,  especially  the  cerebellum 
and  neurone  groups  in  connection  with  it. 


520 


TEXT-BOOK  OF  EMBRYOLOGY. 


entiating  formatio  reticularis,  until  they  are  arrested  at  the  septal  marginal  layer 
(Figs.  454  and  455). 

From  these  neuroblasts  which  remain  in  situ  near  the  dorsal  border  are  de- 
veloped the  nucleus  gracilis  and  nucleus  cuneatus.  The  axones  of  these  nuclei 
form  internal  arcuate  fibers  which  decussate  and  form  a  bundle  of  longitudinal 
fibers  in  the  opposite  septal  marginal  layer  ventral  to  the  reticularis  alba. 
This  tract  is  the  medial  fillet  whose  fibers  appear  during  the  second  month 
and  is  one  of  the  afferent  paths  to  suprasegmental  structures  (mid-brain  roof 


Inner  rhombic  furrow 

Rhombic  lip 
Outer  rhombic  furrow 
Alar  plate] 
Sulcus  limitans 

Tractus  solitarius 
Inner  layer 

N.  X  (medullary  XI) 
Mantle  layer 
Marginal  layer 

Basal  plate 

Beginning  of  gray 
reticular  formation 


Floor  plate  F.r.a.  N.  XII  Internal  arcuate  fibers 

(forming  septum  medullas) 

FIG.  452. — Half  of  a  transverse  section  of  the  medulla  of  a  9.1  mm.  human  embryo 

(during  the  fifth  week).     His. 
The  'arrow  is  in  the  inner  median  sulcus.     F.  r.  a.,  beginning  of  white  reticular  formation. 

and  pallium).  Other  neuroblasts,  which  probably  migrate  further,  form  the 
substantia  gelatinosa  of  Rolando.  Axones  of  this  group  also  form  tracts  repre- 
senting afferent  paths  to  suprasegmental  structures  (pallium).  Neuroblasts 
which  migrate  further  form,  as  already  mentioned,  afferent  cerebellar  con- 
nections. Those  migrating  to  the  septal  marginal  layer  form  there  an 
L-shaped  mass  mesial  to  the  root  fibers  of  the  XII  cranial  nerve  (Fig.  455). 
This  is  the  medial  accessory  olive.  Fresh  groups  of  neuroblasts,  added  laterally 
to  these  in  streaks,  form  the  inferior  olivary  nucleus,  while  others  which  have  not 
advanced  so  far  form  the  lateral  nucleus.  Axones  of  the  olivary  neuroblasts 


THE  NERVOUS  SYSTEM. 


521 


(olivo-cerebellar  fibers)  pass  across  the  median  line  (seventh  or  eighth  week)  to 
the  opposite  dorsal  border  where  they,  together  with  axones  from  the  lateral 
nuclei  and  the  continuation  from  the  cord  of  Flechsig's  tract,  form  (end  of 
the  second  month)  the  bulk  of  the  restiform  body  (Fig.  455).  At  three  months 
the  olives  have  acquired  their  characteristic  folded  appearance. 

Owing  to  the  later  development  and  ventral  migration  of  the  alar  plate 
r.euroblasts,  there  are  thus  formed  the  various  nuclei  which  lie  external  to  the 
i^ticular  formation  in  the  adult.  The  continuations  of  ascending  spinal  >:ord 


Outer  part  of  rhombic 
lip  migration 

Inner  part  of  r.  1.  mig. 
Inner  layer 
Tractus  solitarius 
Marginal  layer 
Mantle  layer 

Ext.  arcuate  fibers 
Int.  arcuate  fibers 


Septum      Beginning  white        N.  XII      Gray  reticular 
medullae    reticular  formation  formation 

FIG.  453. — Half  of  a  transverse  section  of  the  medulla  of  a  10.5  mm.  human  embryo 
(end  of  fifth  week).     His. 

tracts  (Flechsig  and  Gowers)  occupy  the  most  external  position  on  the  lateral  sur- 
face, and  other  cord  continuations  (medial  fillets)  the  most  external  mesial 
positions.  Later,  however  (fifth  month),  there  is  added  ventral  to  the  fillets 
the  descending  cortico-spinal  fibers  (pyramids).  Their  decussation  takes 
place  at  the  cervical  flexure. 

By  the  external  accessions  from  the  alar  plate  above  described,  forming 
terminal  nuclei  of  overlapping  tracts  from  above  (especially  the  nucleus  of 
the  spinal  V),  the  tractus  solitarius  becomes  buried,  as  it  were,  hence  its  deep 
position  in  the  adult.  The  great  development  of  the  reticular  formation 
may  contribute  to  this  result.  As  the  trigeminus  is  the  most  cephalic  rhombic 


522 


TEXT-BOOK  OF  EMBRYOLOGY. 


segment,  its  descending  fibers  are  not  overlapped  by  fibers  from  above  and 
therefore  occupy  the  most  external  position  of  all  these  descending  peripheral 
systems. 

Mantle  layer  Inner  layer       Gray  ret.  form 

\       ^JiiiiiiifK         / 


'^^fe^^^fe-/^^^ 

53«^*ri^*eLri«s*  _    .  •   -S^S^iSjajj;-.-  ':  .X  X;  'x-^''^ 

^^    ~:r  ^5CV^^^ 


F.r.a. 


Restiform  furrow 

Rhombic  lip  migration  | 

Ext.  arc.  fib.  in  marg.  layer       N.  XII        F.r.a.v.        Septum  medullas 

FIG.  454. — Half  of  a  transverse  section  through  the  medulla  of  a  13.6  mm.  human  embryo 

(beginning  of  sixth  week).     His. 

F.  r.  a.,  Beginning  of  white  reticular  formation  in  dorsal  part  of  septal  marginal  layer. 
Another  bundle  has  formed  more  ventrally  (F.  r.  a.  v.) . 


Inner  layer 


Roof  plate 


Tractus  solitarius 


Formatio  reticularis 
grisea 


Formatio  reticularis  alba 


N.  XII  Septum 

medullse 


Spinal  V 

Neuroblasts  from  alar  plate 
Marginal  layer 


Neuroblasts  from  alar  plate 
(Rudiment  of  accessory  olive) 


FIG.  455. — Transverse  section  through  the  medulla  of  an  8  weeks'  human  embryo.     His. 

The  terminal  nuclei  belonging  to  the  auditory  (acustico-facialis-abducens) 
segment  are  those  of  the  vestibular  and  cochlear  portions  of  the  VIII  nerve. 


THE  NERVOUS  SYSTEM.  523 

The  development  of  these  nuclei  is  not  fully  known,  but  they  are  derived  from 
the  alar  plate,  except  possibly  Deiters'  nucleus  (see  p.  517),  the  nuclei  of  the 
later  formed  cochlear  nerve  occupying  the  more  external  position.  The  ves- 
tibular nuclei  apparently  send  axones  both  to  cerebellum  and  reticular  formation. 
The  cerebellum  itself  may  be  regarded  as  primitively  a  receptive  vestibular 
structure  (p.  466)  and  probably  receives  vestibular  root  fibers.  The  axones 
of  the  cochlear  nuclei  pass  across  the  median  line,  along  the  ventral  border  of 
the  reticular  formation  (second  half  of  second  month),  forming  the  trapezium. 
On  the  lateral  boundary  of  the  opposite  reticular  formation  they  ascend,  form- 
ing the  lateral  fillet,  to  the  suprasegmental  posterior  corpus  quadrigeminum. 
Accessions  are  received  from  the  superior  olive,  in  which  some  of  the  trapezium 
fibers  terminate. 

The  alar  plate  of  this  segment  also  forms  the  substantia  gelatinosa  and  the 
anterior  portions  of  the  olivary  nuclei  in  this  region.  The  various  remaining 
tracts  assume  the  same  positions  as  further  caudally. 

Later,  the  pyramids  are  added  ventrally  to  the  fillet,  and  the  great  develop- 
ment of  the  pons  leads  to  its  covering  the  ventral  surface  of  part  of  this  region. 
Owing  to  the  late  development  of  the  pons  and  pyramids,  the  trapezium  is  thus 
uncovered  and  lies  on  the  ventral  surface  of  the  rhombic  brain  during  the  third 
month.  It  is  permanently  uncovered  in  the  dog  and  cat. 

In  the  trigeminus  segment,  the  terminal  nucleus  of  the  afferent  portion  of 
this  nerve  is  probably  similarly  formed  from  the  alar  plate.  Its  axones  decus- 
sate, probably  joining  the  fillet,  and  proceed  to  the  thalamus,  which  is  connected 
with  the  pallium.  Descending  axones  from  cells  in  the  mid-brain  roof  form 
part  of  the  trigeminus  known  as  its  descending  or  mesencephalic  root.  The 
view  has  been  advanced  (Meyer,  Johnston)  that  these  are  afferent  neurones 
equivalent  to  certain  dorsal  horn  cells  found  in  some  adult  and  embryonic 
Vertebrates  and  representing  spinal  ganglion  cells  which  have  become  included 
in  the  neural  tube  instead  of  becoming  detached  with  the  rest  of  the  neural  crest 
(compare  p.  452). 

In  front  of  the  lateral  recess  another  extensive  development  of  the  alar  plate 
occurs,  evidenced  by  the  large  rhombic  lip  of  this  region.  The  neuroblasts 
thus  differentiated  form  the  enormously  developed  pontile  nuclei  whose  axones 
pass  across  the  median  line  (fifth  month)  to  the  opposite  cerebellar  hemisphere, 
forming  the  middle  cerebellar  peduncle  or  brachium  pontis.  The  pons  extends 
over  the  ventral  surface  of  the  cephalic  part  of  the  medulla  and  over  the  ventral 
surface  of  part  of  the  mid-brain.  It  receives  fibres  from  various  parts  of  the 
neopallium,  which  form  a  great  part  of  the  pes  pedunculi  or  crusta.  A  still 
greater  development  of  the  alar  plate  forms  the  cerebellum. 

In  the  mid-brain  region,  the  reticular  formation  already  described  (p.  517) 
is  enveloped  ventrally  and  laterally  by  the  upward  extension  of  the  medial  and 


524  TEXT-BOOK  OF  EMBRYOLOGY. 

lateral  fillets,  the  whole  comprising  the  tegmentum.  Ventral  to  this  are  added 
later  the  pons  and  the  descending  cortico-pontile,  cortico-bulbar  and  cortico- 
spinal  bundles  forming  here  the  pes  pedunculi  or  crusta  (probably  during  the 
fifth  month). 

The  alar  plate  of  the  mid-brain  region  forms  the  corpora  quadrigemina 
(mid-brain  roof). 

The  further  changes  in  the  gross  morphology  of  the  medulla  are  due  mainly 
to  further  growth  of  structures  already  present.  The  nuclei  of  the  dorsal  col- 
umns by  their  increase  cause  the  swellings  on  the  surface  of  the  medulla  known 
as  the  clava  and  cuneus,  and  likewise  by  their  increase  in  size  cause  a  secondary 
dorsal  closing  in  of  the  caudal  apex  of  the  fourth  ventricle  which  formerly 
extended  to  the  cervical  flexure.  The  tuber culum  of  Rolando  is  produced  by  the 
growth  of  the  terminal  nucleus  of  the  spinal  V,  and  the  restiform  body  largely 
by  the  development  of  the  afferent  cerebellar  fibers  (Fig.  457). 

The  growth  of  the  olivary  nuclei  produces  the  swellings  known  as  the 
olives.  The  above  mentioned  accession  of  the  descending  cerebrospinal  tracts 
to  the  ventral  surface  is  indicated  by  the  pyramids. 

In  the  floor  of  the  ventricle  there  is  a  longitudinal  ridge  each  side  of  the 
median  line  occupied  by  swellings  produced  by  the  nucleus  of  the  XII  and, 
further  forward,  the  nucleus  of  the  VI,  together  with  other  nuclei  (intercalatus, 
funiculus  teres  and  incertus,  Streeter)  which  are  not  well  understood.  The 
furrow  forming  the  lateral  boundary  of  this  area  is  usually  taken  to  be  the 
representative  of  the  sulcus  limitans  and  consequently  the  area  in  question 
would  be  the  basal  plate.  Lateral  to  it  is  a  triangular  area  with  depressed 
edges — the  ala  cinerea.  It  represents  a  region  where  portions  of  the  vago- 
glossopharyngeal  nuclei  (dorsal  efferent  and  terminal  nuclei  of  fasciculus 
solitarius)  lie  near  the  surface.  Possibly  a  secondary  invasion  by  surrounding 
more  recently  differentiated  nuclei  may  account  for  their  apparent  partial 
retreat  from  the  surface.  It  is  possible  that  the  ala  cinerea  may  be  regarded 
not  so  much  as  a  part  of  the  alar  plate,  but  that  it — or  rather  the  branchial 
nuclei  involved  in  its  formation — represents  an  independent  intermediate  region 
corresponding  to  the  intermediate  region  in  the  cord  (J.  T.  Wilson).  The 
remaining  portion  of  the  alar  plate,  in  the  floor,  is  apparently  represented 
principally  by  the  acoustic,  especially  the  vestibular,  field. 

In  the  development  of  the  segmental  brain  there  are  thus  the  following 
overlapping  stages:  (i)  The  differentiation  of  the  inner,  mantle  and  marginal 
layers.  (2)  The  prima^v  neural  apparatus,  consisting  of  (a)  the  peripheral 
segmental  neurones,  the  central  processes  of  the  afferent  neurones  entering  the 
alar  or  receptive  plate,  the  efferent  neurone  bodies  forming  two  main  series 
of  nuclei  in  the  basal  plate,  and  (b)  intersegmental  neurones  composing  the 
reticular  formation  in  which  the  long  tracts  occupy  external  positions.  (3) 


THE  NERVOUS  SYSTEM. 


525 


The  further  differentiation,  from  the  alar  plate,  of  terminal  nuclei  for  the 
afferent  peripheral  segmental  neurones,  the  axones  of  the  terminal  nuclei 
forming  afferent  tracts  to  suprasegmental  structures.  These  tracts  and  other 
later  forming  afferent  suprasegmental  tracts  with  their  nuclei  are  laid  down 
ext(  rnal  to  the  reticular  formation.  (4)  Formation  of  efferent  (chiefly  th  ala- 
mic(?)  mid-brain  and  cerebellar)  suprasegmental  tracts  which  act  upon  the 
intersegmental  neurones  or  reticular  formation.  (5)  Accession  at  a  late  s';age 
of  d  svelopment  of  a  descending  system  of  fibres  from  the  neopallium.  T.'iese 
lie  's  entral  to  the  preceding  structures. 


The  Cerebellum. 

It  has  already  been  pointed  out  that  at  an  early  period  (three  weeks)  the 
anterior  boundaries  of  the  thin  expanded  roof  plate  of  the  rhombic  brain  form 
two  lines  converging  anteriorly  to  the  median  line  where 
the  roof  plate  is  represented  by  the  usual  narrow  portion 
connecting  the  two  alar  plates  (Fig.  456).  It  has  also 
been  pointed  out  that  the  pontine  flexure  produces  on  the 
dorsal  surface  a  deep  transverse  fold  in  this  thin  roof,  into 
which  vascular  tissue  grows  later  forming  the  chorioid 
plexus  (Fig.  448) .  At  this  stage,  the  continuations  of  the 
alar  plates  of  the  medulla  form  two  transverse  bands 
which,  when  viewed  laterally,  are  vertical  to  the  general 
longitudinal  axis  of  this  part  of  the  brain  (Fig.  448) .  At 
the  same  time,  the  rhombic  lips  are  formed  along  the 
caudal  border  of  these  bands  and  the  latter  become 
thickened  into  the  two  rudiments  of  the  cerebellum,  a 
considerable  portion  of  which  may  be  derived  from  the 
lips.  These  rudiments  are  thus  two  transverse  and 
vertical  swellings  and  are  connected  across  the  median 
line  by  the  roof  plate.  The  attachment  (taenia)  of  the 
alar  plate  of  this  region  to  the  roof  plate  of  the  fourth 
ventricle  is  at  first  along  its  caudal  edge.  Later,  by  the 
folding  back  and  fusion  of  this  border  to  form  the  rhom- 
bic lips,  the  attachment  is  carried  forward.  Still  later, 
by  the  growth  of  the  cerebellar  rudiment,  it  is  rolled 
backward  and  under,  as  described  below.  The  rudi- 
ments subsequently  fuse  across  the  median  line,  thus 
forming  externally  a  single  transverse  structure,  but  internally  a  paired  dorsal 
median  projection  of  the  lumen  marks  the  location  of  the  uniting  roof  plate 
(comp.  Fig.  458). 


FIG.  456. — Dorsal  view 
of  that  part  of  the 
brain  caudal  to  the 
cephalic  flexure 
(human  embryo  of  3d 
week,  2.15  mm.).  Hh. 
Cerebellum;  J,  isth- 
mus; M,  mid-brain; 
Rf,  A7z,  medulla. 
Compare  with  Fig. 
416.  His. 


526 


TEXT-BOOK  OF  EMBRYOLOGY. 


While  the  structure  thus  formed  expands  enormously  in  a  lateral  direction, 
in  its  subsequent  development  its  greatest  growth  is  in  a  longitudinal  direction. 
The  effect  of  this  is  that  the  continuations  of  the  cerebellum  forward  (velum 
medullare  anterius}  and  backward  (velum  medullare  posterius)  into  the  adjoining, 
brain  walls  of  the  isthmus  and  medulla  are  comparatively  fixed  points  and  are 
completely  overlapped  by  the  spreading  cerebellum,  producing  an  appearance 
in  sagittal  section  as  though  they  were  rolled  in  under  the  latter  structure  (comp. 
Fig.  408,  F) .  Another  result  of  this  longitudinal  growth  is  the  formation  of  fis- 
sures running  across  the  organ,  transversely  to  the  longitudinal  brain  axis. 
First,  lateral  incisures  separate  two  caudal  lateral  portions,  the  flocculi  (Fig. 
457),  the  median  continuation  of  which,  the  nodule,  is  finally  rolled  in  on 
the  under  side  of  the  cerebellum  as  explained  above.  Another  transverse  fissure, 
the  primary  fissure,  beginning  in  the  median  part  and  extending  laterally,  sepa- 

^^^^  Cerebellar  hemisphere 

Tasnia 

Tuberculum  cuneatum  — 
Cla- 

Tuberculum  cinereum  (Rolando) 


• —  Fasciculus  gracilis  (Goll) 

•  Fasciculus  cuneatus  (Burdach) 


FIG.  457. — Dorsal  view  of  the  cerebellum  and  medulla  of  a  5  months'  human  foetus.     Kollmann. 

rates  an  anterior  lobe  from  a  middle  lobe,  the  former  comprising  the  future  lin- 
gula,  centralis  and  culmen  and  their  lateral  extensions.  The  anterior  portion 
is  rolled  forward  under  the  anterior  part  of  the  cerebellum.  Another  trans- 
verse fissure  next  appears  in  the  median  part  (secondary  fissure)  which  later  ex- 
tends (peritonsillar)  to  the  floccular  incisure,  and  thereby  completes  the  de- 
marcation of  a  posterior  lobe,  including  not  only  the  flocculus  and  nodule,  but 
also  the  tonsilla  and  uvula,  which  are  also  rolled  backward  and  under.  The 
result  of  this  transverse  fissuration  would  be  the  production  of  a  cerebellum 
resembling  that  of  certain  forms  below  Mammals  where  the  cerebellum  is  well 
developed  (Selachians,  Birds).  A  complicating  factor,  however,  is  the  great 
growth  of  certain  lateral  portions  of  the  middle  lobe,  forming  the  future  cere- 
bellar  hemispheres  (Fig.  457),  which  causes  also  a  lateral  overlapping  and  rolling 
inward  of  adjoining  parts.  This  growth  is  the  chief  factor  in  the  division 
of  the  cerebellum  into  vermis  and  hemispheres  and  is  correlated  with  the  devel- 
opment of  the  neopallium  (p.  466  and  Fig.  409). 


THE  NERVOUS  SYSTEM. 


527 


The  early  histological  development  of  the  cerebellum  has  been  most  closely 
studied  in  Bony  Fishes  (Schaper)  and  there  is  every  reason  to  suppose  that 
the  processes  taking  place  in  the  human  cerebellum  are  essentially  the  same.  In 
that  part  of  the  alar  plate  forming  the  rudiment  above  described,  the  cells  pro- 
liferate, forming  first  a  nuclear  layer  with  the  dividing  cells  along  its  ventricular 
surface,  and  a  non-nucleated  outer  or  marginal  layer.  Later,  owing  to  begin- 
ning migration  and  differentiation,  there  is  formed  the  usual  mantle  layer, 
representing  a  differentiation  of  part  of  the  original  nuclear  layer  and  thereby 
forming  the  three  layers:  an  inner,  a  mantle  and  a  marginal.  The  outer  cells 
of  the  mantle  layer  increase  in  size  and  differentiate  into  the  cells  of  Purkinje, 
snaller  cells  within  forming  the  granular  layer.  The  earliest  stage  of  differ- 
entiation of  the  Purkinje  cells  has  not  been  accurately  described,  but  the  axones 


FIG.  458. — Diagram  representing  the  differentiation  and  migration  of  the  cerebellar  cells  in  a  teleost. 
The  arrows  indicate  the  migration  of  cells  from  the  borders  of  the  cerebellar  rudiment  into 
the  marginal  layer;  these  cells  probably  all  differentiate  into  nerve  cells.  Clear  circles,  indif- 
ferent cells;  circles  ivith  dots,  neuroglia  cells  (except  in  marginal  layer);  shaded  cells,  epithelial 
cells;  circles  with  crosses,  epithelial  cells  in  mitosis  (germinal  cells) ;  black  cells,  neuroblasts;  L 
lateral  recess;  A/,  median  furrow,  above  which  is  roof  plate;  R,  floor  of  4th  ventricle  (IV). 
Schaper. 

of  the  neuroblasts  evidently  proceed  (end  of  fifth  month)  toward  the  ventricular 
surface  instead  of  entering  the  marginal  layer.  In  this  way  the  fibrous  layer 
(white  matter)  comes  to  lie  within  instead  of  on  the  outer  surface  as  in  the  cord, 
and,  to  some  extent,  in  the  medulla.  There  is  thus  formed  the  outer  gray  matter 
or  cortex.  The  axones  of  the  Purkinje  cells  form  the  great  bulk  of  the  centrifu- 
gal fibers  of  the  cerebellar  cortex.  The  marginal  layer  becomes  ultimately 
the  outer  or  molecular  (plexiform)  layer  of  the  adult  cerebellum. 

It  has  been  seen  that  in  the  other  parts  of  the  tube  development  begins  in 
the  medial  parts  of  the  lateral  plates  and  thence  advances  toward  their  dorsal 
borders,  which  actively  develop  after  the  corresponding  stages  have  ceased  in 
the  medial  portions.  The  same  is  true  of  the  cerebellar  rudiment.  In  this, 
the  edges  which  border  on  the  thin  roof  plate,  i.e.,  those  parts  adjoining  the 
lateral  recesses,  the  main  roof  of  the  fourth  ventricle  and  the  roof  plate  inter- 
posed between  the  two  original  lateral  cerebellar  rudiments,  are  the  last  to  pro- 


528 


TEXT-BOOK  OF  EMB.RYOLOGY. 


liferate.  The  cells  thus  formed  spread  into  the  marginal  layer  of  the  earlier 
developed  parts  and  by  further  proliferation  form  a  nucleated  layer  of  consider- 
able thickness  (Fig.  458).  This  complication  is  apparently  essentially  similar 
to  that  described  above  in  the  development  of  the  medulla.  From  the  cells  of 
this  invasion  are  formed  a  part,  at  least,  of  the  granule  cells,  as  well  as  the  basket 
cells  and  other  cells  which  remain  in  the  marginal  (molecular)  layer.  These 
are  all  association  cells  of  the  cerebellum. 

The  cerebellum  reaches  its  full  histological  development  very  late;  after 
birth  in  many  Mammals.     These  last  postnatal  stages  of  development  naturally 


FIG.  459. — Scheme  showing  the  various  stages  of  position  and  form  in  the  differentiation  of  granule 
cells  from  the  outer  granular  layer.  Cajal. 

At  Layer  of  undifferentiated  cells;  B,  layer  of  cells  in  horizontal  bipolar  stage;  C,  partly  formed 
molecular  (plexiform)  layer;  D,  granular  layer;  b,  beginning  differentiation  of  granule  cells; 
c,  cells  in  mono  polar  stage;  d,  cells  in  bipolar  stage;  e,f,  beginning  of  descending  dendrite 
and  of  unipolarization  of  cell;  g,h,  i,  different  stages  of  unipolarization  or  formation  of  single 
process  connecting  with  the  original  two  processes;  j,  cell  showing  differentiating  and  com- 
pleted dendrites;  k,  fully  formed  granule  cell. 

involve  principally  those  cells  proliferated  last  and  which  lie  in  the  mar- 
ginal layer.  These  have  been  studied  by  means  of  the  Golgi  method  in 
new-born  Mammals  by  Cajal  and  others.  The  majority  of  these  cells  form 
granule  cells  by  means  of  a  progressive  migration  and  differentiation,  as  shown 
in  the  accompanying  Fig.  459.  Each  cell  first  develops  a  single  horizontal 
process,  then  another,  thus  becoming  a  horizontal  bipolar  cell.  Following  this, 
the  cell  body  migrates  past  the  Purkinje  cells  into  the  granular  layer,  remaining 
in  connection  with  the  original  processes  by  a  single  process.  There  are  thus 
formed  the  axone  of  the  granule  cell  with  its  bifurcation  into  two  horizontal  pro- 
cesses, the  parallel  fibers  of  the  molecular  layer.  This  mode  of  formation  is  thus 


THE  NERVOUS  SYSTEM.  529 

similar  to  the  unipolarization  of  the  cerebrospinal  ganglion  cell.  The  dendrites 
begin  to  be  formed  during  the  migration,  branch  when  the  cell  body  reaches  the 
granular  layer  and  there  finally  attain  the  adult  form.  Other  undifferentiated 
cells  in  the  marginal  layer  send  out  horizontal  processes  the  collaterals  of  which 
envelop  the  Purkinje  cell  bodies,  and  form  the  baskets.  The  place  vacated,  so  to 
speak,  by  the  migrating  granules,  is  filled  at  the  same  time  by  the  developing 
dendrites  of  the  Purkinje  cells.  These  at  first  show  no  regularity  of  branching, 
but  subsequently  differentiate  into  the  definite  branches  of  the  adult  condition, 
at  fhe  same  time  advancing  toward  the  periphery  (Fig.  460).  When  they 


FIG.  460. — Section  through  cerebellar  cortex  of  a  dog  a  few  days  after  birth,  showing  the  partial 
development  of  the  dendrites  of  two  cells  of  Purkinje.  Cajal. 

A,  external  limiting  membrane;  B,  external  (embryonic)  granule  layer;  C,  partly  formed  molecular 
(plexiform)  layer;  D,  granular  layer;  a,  body  of  cell  of  Purkinje;  b,  its  axone;  c,  and  d,  col- 
laterals with  terminal  arborizations  (e). 

reach  this,  the  migration  of  the  granules  is  completed  and  the  molecular  layer 
is  definitely  formed.  This  condition,  evidenced  by  the  disappearance  of  the 
outer  granular  layer,  is  usually  reached  in  Mammals  within  two  months  after 
birth,  but  in  man  not  until  the  sixth  or  seventh  year.  There  are  observations 
indicating  that  animals  possessing  completely  developed  powers  of  locomotion 
and  balancing  at  birth  have  more  completely  differentiated  cerebella  at  that 
time.  The  axones  of  the  Purkinje  cells  form  many  embryonic  collaterals  which 
are  afterward  reduced  in  number. 

Of  the  centripetal  fibers  to  the  cerebellum,  those  from  the  inferior  olives 
.cross  the  median  line  of  the  medulla  about  the  seventh  or  eighth  week,  and 
thence  advance  to  the  vermis,  reaching  their  final  destination  during  the  third 


530  TEXT-BOOK  OF  EMBRYOLOGY. 

month.  The  fibers  from  the  pontile  nuclei  (middle  peduncle)  do  not  develop 
until  considerably  later  (end  of  the  fourth  month),  the  time  of  their  reaching 
their  destination  in  the  cerebellar  hemispheres  not  being  definitely  known. 
Many  at  least  of  the  centripetal  fibers  do  not  reach  their  full  development  in 
Mammals  till  birth  or  after.  Some  of  these  fibers  (climbing fibers]  form  arbor- 
izations around  the  inferior  (axone)  surface  of  the  Purkinje  cell  bodies  and 
later  creep  upward,  enveloping  the  upper  surface  instead,  and  finally  the  den- 
dritic branches.  Other  centripetal  fibers  (mossy  fibers)  ramifying  in  the 
granular  layer  are  varicose  fibers,  at  first  otherwise  smooth.  From  the  vari- 
cosities  a  number  of  branches  are  given  off  which  later  become  abbreviated  and 
modified  into  the  shorter  processes  of  the  adult  condition.  This  final  differ- 
entiation occurs  simultaneously  with  the  final  differentiation  of  the  dendrites 
of  the  granule  cells  with  which  they  come  into  connection.  The  glia  elements 
apparently  develop  in  a  manner  essentially  similar  to  their  development  else- 
where. 

The  development  of  the  internal  nuclei  of  the  cerebellum  has  not  been 
thoroughly  investigated.  The  nucleus  dentalus  is  well  developed  at  the  end 
of  the  sixth  fcetal  month.  Eminences  passing  forward  and  ventrally  along 
the  sides  of  the  isthmus  are  the  earliest  indications  of  the  superior  peduncles^ 
formed  later  by  the  axones  of  the  cells  of  these  nuclei. 

Corpora  Quadrigemina. 

The  mid-brain  roof  is  an  expansion  of  the  alar  plate  of  the  mid-brain. 
Later  this  differentiates  into  the  anterior  and  posterior  corpora  quadrigemina. 
In  the  former,  by  the  usual  ventricular  mitoses  (germinal  cells),  a  nuclear 
layer  is  formed  with  a  non-nucleated  marginal  layer  external  to  it  which  becomes 
the  outer  or  zonal  layer.  Still  later  the  neuroblast  or  mantle  layer  is  differen- 
tiated, there  being  an  unusually  thick  inner  layer.  The  further  development 
has  not  been  closely  studied  in  man.  Owing  to  the  diminished  importance 
of  the  anterior  corpora  quadrigemina  (p.  467)  the  neuroblasts  do  not  differ- 
entiate into  the  well  marked  "spread  out"  layers  characteristic  of  the  optic 
lobes  of  many  Vertebrates.  This  is  probably  due  to  a  lack  of  development  of 
their  association  neurones. 

The  fibers  of  the  optic  tracts  grow  toward  the  anterior  corpora  quadrigemina 
in  the  marginal  layer  forming  the  anterior  brachia.  When  they  reach  the 
anterior  corpora  quadrigemina,  they  leave  the  marginal  layer  and  penetrate 
the  gray  matter  forming  the  most  external  fiber  layer.  The  medial  (and  some 
lateral)  lemniscus  fibers  enter  more  deeply  than  the  optic.  Neuroblast  axones 
grow  toward  the  ventricle,  turn  internally  to  the  lemniscus  fibers,  cross  (Mey- 
nerfs  decussatiori) ,  and  proceed  as  the  predorsal  tracts  to  the  segmental  brain 
and  cord,  lying  ventral  to  the  medial  longitudinal  fasciculi. 


THE  NERVOUS  SYSTEM.  531 

The  Diencephalon. 

The  stage  of  development  of  the  diencephalon  at  four  weeks  has  already 
been  mentioned  (p.  478).  (Figs.  461,  471  and  472.)  In  the  lateral  walls  the 
principal  feature  is  the  presence  of  a  furrow,  the  sulcus  hypothalamicus,  which 
beg;ns  ventrally  as  an  extension  of  the  optic  recess  and  extends  dorsally  and 
caudally  toward  the  mid-brain.  A  branch  of  it  extends  to  the  posterior  part 
of  the  foramen  of  Monro.  This  is  the  sulcus  Monroi.  The  sulcus  hypothala- 
micus is  sometimes  regarded  as  the  representative  in  this  region  of  the  sulcus 
limi  tans.  It  is  doubtful  whether  it  has  the  same  morphological  value  as  the 
latter.  Such  a  comparison  is  seen  a  priori  to  be  difficult  when  it  is  considered 
that  this  region  is  in  the  most  highly  modified  part  of  the  brain  tube,  lacking 


SM 


Ma. 


FIG.  461. — Transverse  section  through  the  diencephalon  of  a  5  weeks'  human  embryo.  Dp.,  Roof 
plate;  Ma.,  mammillary  recess;  P.  s.  hypothalamus;  S.M.,  sulcus  hypothalamicus;  Th.t 
thalamus.  His. 

motor  peripheral  apparatus,  and  that  it  is  also  the  end  region  of  the  tube  where 
all  longitudinal  divisions  would  naturally  merge.  The  sulcus  deepens  till  the 
end  of  the  second  month  (Fig.  467).  Later  it  becomes  shallower,  but  appears 
to  persist  till  adult  life.  The  region  of  the  diencephalon  ventral  to  the  sulcus, 
as  already  mentioned,  is  termed  the  pars  subthalamica  or  hypothalamus.  The 
ventral  part  of  the  optic  stalk  forms  a  transverse  groove  in  the  floor,  the  pre- 
optic  recess,  caudal  to  which  is  a  ridge  or  fold,  the  chiasma  swelling,  in  which  the 
fibers  of  the  optic  chiasma  later  appear.*  Caudal  to  this  is  the  recess  or  invagi- 
nation  of  the  floor,  representing  the  postoptic  recess  and  the  beginning  of  the 
infundibulum  (Figs.  462  and  463) .  Its  extremity  later  becomes  extended  into  the 
infundibular  process,  the  posterior  part  of  which  in  the  fifth  week  comes  into 
contact  with  the  hypophyseal  (Rathke's)  pouch.  This  is  a  structure  formed 

*  According  to  Johnston,  the  chiasma  is  formed  in  front  of  the  optic  recess  which  would  then  be 
represented  by  the  postoptic  recess.  In  this  case  the  chiasma  would  be  regarded  as  falling  in  the 
region  of  the  telencephalon  instead  of  forming  the  optic  part  of  the  hypothalamus  (comp.  Figs.  402 
and  471). 


532 


TEXT-BOOK  OF  EMBRYOLOGY. 


from  the  stomodaeal  epithelium  and  is  connected  with  the  latter  by  a  stalk. 
The  pouch,  which  is  at  first  a  flat  structure,  develops  two  horns  which  envelop 


Ant.  corp.  quad.    Pineal 
(ant.    colliculus)    region 


Anterior 
brachium 


r> 
w 


•^>' 


Pallium 


Ant 


olfact.  lobe 


Post. 
Optic  stalk 
Hypophyseal  pouch 


Mammillary    Lateral         Tuber 
region        geniculate    cinereum 
body 

FIG.  462. — Lateral  view  of  a  model  of  the  brain  of  a  10.2  mm.  human  embryo 
(middle  of  5th  week).     His. 

the  infundibulum.  The  cavity  of  the  end  of  the  infundibular  process  becomes 
nearly  shut  off  from  the  rest  of  the  infundibular  cavity.  The  process  penetrates 
the  upper  part  of  the  pouch  and  then  bending  reaches  its  posterior  surface  and 

Diencephalon        Thalamus  Pineal  region 


Pallium 

Foramen  of  Monro 

Sulcus  hypothal- 
amicus 

Ant.  olfact.  lobe 

Post,  olfact.  lobe 

Lamina  terminalis 

Corpus  striatum 


Mesencephalon 
Tegmental  swelling 

Mammillary  region 
Hypothalamus 
Tuber  cinereum 


Recessus      Hypophyseal      Recessus 
(prae?)  opticus        pouch  infundibuli 

FIG.  463. — Median  view  of  the  right  half  of  a  model  of  the  brain  of  a  10.2  mm.  human  embryo 
(middle  of  5th  week).     Compare  Fig.  462.     His. 

ends  blindly.     In  the  second  half  of  the  second  month  epithelial  sprouts,  which 
become  very  vascular,  begin  to  appear,  first  in  the  lateral  parts  of  the  pouch, 


THE  NERVOUS  SYSTEM.  533 

next  the  brain,  and  then  extending  through  the  pouch  and  finally  nearly  oblit- 
erating its  cavity  (third  month).  The  shape  of  the  organ  (the  hypophysis) 
formed  by  the  union  of  these  two  parts  is  subsequently  changed  by  its  relations 
to  surrounding  parts.  Its  posterior  lobe  is  derived  from  the  infundibular  por- 
tiDn,  its  anterior  lobe  from  the  pouch. 

An  expansion  of  the  floor  of  the  brain  caudal  to  the  infundibulum  has  been 
mentioned  as  the  mammillary  region.  Subsequently  there  is  formed  fror.i  its 
ce  phalic  part  another  evagination,  the  tuber  cinereum.  The  mammillary  region 
forms  the  mammillary  bodies.  The  region  caudal  to  the  mammillary  region 
la';er  receives  many  blood  vessels,  thereby  becoming  the  posterior  perforated 
space. 

At  the  end  of  the  fourth  week  the  roof  plate  of  the  diencephalon  is  smooth. 
At  about  this  time  the  greater  part  of  the  roof  expands,  forming  a  median 
longitudinal  ridge  (Fig.  464).  This  ridge,  which  remains  epithelial  throughout 
life,  is  broader  at  its  anterior  end  where  it  passes  between  the  beginning  pallial 
hemispheres.  As  the  roof  plate  expands  further,  the  anterior  part  is  next 
thrown  into  longitudinal  folds.  The  ridge  forms  the  epithelial  lining  of  the 
tela  chorioidea  of  the  third  ventricle  (diatela).  By  further  growth  and  vas- 
cularization  of  its  mesodermal  covering  at  the  beginning  of  the  third  month, 
there  is  formed  the  chorioid  plexus  of  the  third  ventricle  (diaplexus).  Lateral 
extensions  of  the  tela  form  the  chorioid  plexuses  of  the  lateral  ventricles  (see 
p.  547) .  In  the  fifth  week  a  protrusion  appears  at  the  caudal  end  of  the  median 
ridge  which  is  the  beginning  of  the  epiphysis.  Soon  after  this,  the  furrow  which 
forms  its  caudal  boundary  extends  forward  along  the  upper  part  of  the  sides  of 
the  walls,  marking  off  a  fold  which  is  the  lateral  continuation  of  the  median 
protrusion.  From  the  median  protrusion  is  later  formed  the  pineal  bodyy 
while  from  the  lateral  folds  are  formed  the  pineal  stalk,  and  in  front  the 
habenula,  with  its  contained  nucleus  (ganglion)  habenulce,  and  the  stria 
medullaris.  Still  further  caudally,  the  anterior  part  of  the  mid-brain  forms 
a  horseshoe-shaped  fold  the  arms  of  which  extend  forward  over  the  dien- 
cephalon, ventral  to  the  pineal  folds.  The  median  part  of  this  fold  forms  the 
anterior  corpora  quadrigemina.  From  its  lateral  extensions  are  formed  the 
anterior  brachia  of  the  anterior  corpora  quadrigemina,  the  pulvinar  and  the 
lateral  and  medial  geniculate  bodies,  all  of  which  (pulvinar  ?)  later  receive  optic 
fibers.  The  transverse  furrow  which  forms  the  boundary  between  the  rudi- 
ments of  the  pineal  body  and  of  the  anterior  corpora  quadrigemina  marks  the 
location  of  the  future  posterior  commissure  (Figs.  464,  465  and  466) . 

The  part  of  the  roof  anterior  to  the  pineal  fold,  as  already  stated,  forms  the 
tela  chorioidea  of  the  third  ventricle.  Certain  folds  appear  in  it,  however, 
which  are  more  clearly  indicated  in  later  stages  of  embryonic  development 
than  in  the  adult  and  which  probably  represent  structures  already  mentioned 


534 


TEXT-BOOK  OF  EMBRYOLOGY. 


as  common  to  the  vertebrate  brain  ("cushion"  of  the  epiphysis,  velum  trans- 
versum,  paraphysis  ?)   (p.  454  and  Fig.  402) . 

From  the  above  it  is  evident  that  at  the  close  of  the  fifth  week  the  rudiments 
of  the  various  parts  of  the  diencephalon  are  already  well  marked.  These 
rudiments  are  principally  indicated  by  foldings  of  the  walls,  there  being  no  very 
strongly  marked  differences  of  thickness  except  the  early  differentiation  between 
the  median  and  lateral  plates.  From  this  time  on,  both  general  and  local 

Lamina  terminalis 


Cavity  of  ant.  olfact.  lobe 

Anterior  arcuate  fissure 

Cavity  of  post,  olfact.  lobe 

Chorioid  fold 

Hippocampal  fissure 


Lateral  geniculate  body 


Pineal  region 


Ant.  corp.  quad.  (ant.  colliculus) 
(extending  fprward 
into  ant.  brachium) 


i 


Angulus  praethalamicus 


(a)  (b) 
(c) 


Corpus  striatum 


Roof  plate  of  diencephalon 


FIG.  464. — Dorsal  view  of  a  model  of  the  brain  of  a  13.6  mm.  human  embryo  (beginning  of  6th 
week).  The  dorsal  part  of  the  pallium  on  each  side  has  been  removed.  Compare  with 
Figs.  465  and  466.  His, 

thickenings  of  the  lateral  walls  occur.  This  indicates  a  rapid  proliferation 
of  the  cells,  especially  a  differentiation  of  the  nerve  cells  and  consequent  forma- 
tion of  masses  of  gray  and  white  matter.  Another  factor  affecting  the  dien- 
cephalon is  the  subsequent  growth  backward  over  it  of  the  cerebral 
hemispheres. 

During  the  second  month,  the  lateral  walls  become  thickened,  forming 
a  prominence  on  the  inner  surface  of  each  side.  This  reduces  much  of  the 
cavity  of  the  third  ventricle  to  a  cleft  and  in  the  third  or  fourth  month  a  fusion  of 


THE  NERVOUS  SYSTEM. 


535 


a  portion  of  these  two  projections  takes  place,  forming  the  commissura  mollis 
or  massa  intermedia.     The  condition  at  this  stage  is  shown  in  Fig.  467.     Later 

Ant.  corp.  quad.  Diencephalon 


Tegmental 
swelling 

Mammillary 
body 

Tuber 
cinereum 


Pallium 


Beginning  of 
fossa  Sy-vii 

Ant-  "I  olfact. 
PostJlobe 


Optic  stalk 


Infundibulum       Hypophyseal  pouch. 

FIG.  465. — Lateral  view  of  the  model  of  the  brain  of  a  13.6  mm.  human  embryo  (beginning  of  6th 
week).     F,  Beginning  of  frontal  lobe;  T,  beginning  of  temporal  lobe.     His. 

this  protrusion  thrusts  the  lateral  structures  above  described  (the  pulvinar, 
geniculate  bodies  and  brachia)  to  the  side,  the  cavity  of  the  lateral  geniculate 


Eplthalamus  (Corpus  pinealc) 


Mclathalamus  (Corpora  geniculata) 


Thalaraus 


Fissiira 
chorioidea 


Pallium  . 


Rhiiiencephalon 

Corpus  striatum' 
Sulcus  hypothalamicus     ,        -  '-'' 

Hvpothalamus  •' 
Chiasma  opticum 


.Corpora  quadrigemina 


.Pedunculus  cerebrt 


Cerebellum 
Fos«a  rhoniboidea 


FiG.  466. — From  a  model  of  the  brain  of  a  13.6  mm.  human  embryo,  right  half, 
seen  from  the  left  side.     His,  Spalteholz. 

body  being  obliterated.     The  prominence  itself  extends  to  the  tegmental  swell- 
ing (see  Figs.  467-8)  and  there  thus  arises  the  possibility  of  direct  connections 


536 


TEXT-BOOK  OF  EMBRYOLOGY. 


between  these  two  structures.     There  can,  then,  be  distinguished  in  the  dien- 
cephalon  three  regions,  a  hypothalamic  region,  as  already  described,  an  epithala- 


Hippocampal 
fissure 


Chorioid  fissure 
Angulus  praethalamicus 

Foramen  of  Mon 

Ant.  arcuate  fissure 

Preterminal  area 

Ant.  olfact.  lobe 

Olfactory  nerve 

Post,  olfact.  lobe 


Hypothalamic  region 
Mammillary  region 


Lamina  terminalis 


R.o.        Hypophysis 


FIG.  467. — Median  sagittal  section  of  the  brain  of  a  7^  weeks'  human  embryo.  Aq.  S.,  Aquaeductus 
Sylvii;  C.  e.,  fold  between  mid- and  interbrain;  C.  w.,  commissura  mollis;  C.  s.,  corpus  stri- 
atum;  H.  b.,  tegmental  swelling;  R.g.,  geniculate  recess;  R.i.,  recessus  infundibuli;  R.  o.t 
recessus  (prae-?)  opticus;  S.h.y  habenular  evagination;  5.  M.,  sulcus  hypothalamicus;  S.p., 
pineal  evagination;  T.  T.,  thalamus.  His. 

mic  region  comprising  the  pineal  body,  ganglia  habenulae  and  related  structures, 
and  finally  the  thalamus  proper.     In  the  latter,  the  geniculate  bodies  already 

Ttialauuis 

Epithalamus  (Corpus  ptnealei 

Metathalamus 
(Corpora  geniculaial 


Corpus  striati 


RhinencepUalon     /  .•'    /  / 
Pars  optica  hypothalami     ,''  /'     / 
Chiasma  opticum''  ,'' 
Hypophysis'' 

Pars  maraillaris  hypothalarai' 
Pons  (Varo 


Corpora  quadi  igemtna 

•  Pedunculus  cerebri 

-Cerebelhmi 
---  Fossa  rhomboidea 

•  Medulla  oblongaia 


FIG.  468. — Brain  of  a  human  foetus  in  the  3d  month,  right  half,  seen  from  the  left.     His,  Spalteholz. 


mentioned  constitute  a  metaihalamic  portion,  while  the  portion  derived  from 
the  thickened  part,  which  is  continuous  anteriorly  with  the  corpus  striatum, 


THE  NERVOUS  SYSTEM. 


537 


differentiates  various  nuclei,  especially  those  which  receive  the  general  somatic 
sensory  fibers  (medial  lemniscus  or  fillet) ,  and  other  nuclei  in  relation  to  definite 
centers  of  the  pallium.  The  thalamus  is  thus  strongly  developed,  owing  to  its 
containing  the  nuclei  which  receive  the  general  sensory  (ventro-lateral  nuclei), 
acoustic  (medial  geniculate  bodies),  and  optic  (lateral  geniculate  bodies) 
sys  terns  of  fibers  and  which  in  turn  send  fibers  (thalamic  radiations)  to  the  palli  am. 
These  thalamic  nuclei  do  not  receive  fibers  probably  until  after  the  middle  of  the 
second  month.  About  this  time  the  thalamic  radiations  begin  to  be  for.ned 
from  the  thalamic  nuclei  and  grow  toward  the  corpus  striatum  which  they  rjach 
toward  the  end  of  the  second  month.  With  the  first  appearance  of  the  coi  tical 


TbaJatnus 


Pallium 


BhinencepbaloQ 

Becessus  opticus 

Chiasma  Opticnm    ..'    / 
Recessus  infundibuli  '     / 
Infundibulum 

Pedunculus  cerebri 


Velum  medul- 
lare  an  ten  us 


Cerebellum 
Yen  trie  nlus  quart  us 
Medulla  oblongata 


ponstvaroii]          Myelon-Y^ 
WphalohV 

FIG.  469. — Adult  human  brain,  right  half,  seen  from  the  left,  partly  schematic.     Spalteholz. 


layer  of  the  developing  neopallium  (see  p.  542)  they  penetrate  the  corpus  stria- 
tum and  pass  to  the  cortex,  forming  the  beginning  of  the  internal  capsule,  and 
corona  radiata.  It  has  already  been  pointed  out  (p.  467)  that  the  great  develop- 
ment of  the  thalamus  and  its  radiations  is  more  recent  phylogenetically  and  is 
due  to  the  newly  acquired  connections  with  the  neopallium. 

Before  the  development  of  these  neopallial  connections,  other  tracts  have 
begun  to  appear  which  represent  older  epithalamic  and  hypothalamic  connec- 
tions existing  practically  throughout  the  Vertebrates  (pp.  467  and  468).  Some 
of  the  hypothalamic  connections  are  the  mammillo-tegmental  fasciculus  which 
appears  early  in  the  second  month,  the  ihalamomammillary  fasciculus 
(Vicq  d'Azyr's  bundle),  which  appears  later,  and  the  bundles  from  the  rhinen- 
cephalon  (p.  505)  and  archipallium  (columns  of  the  fornix,  middle  of  fourth 
month,  p.  551).  In  the  hypothalamic  region  is  also  differentiated  the  corpus 


538 


TEXT-BOOK  OF  EMBRYOLOGY. 


Luysii,  connected  by  "fiber  bundles  with  the  corpus  striatum  and  tegmentum. 
Epithalamic  connections  are  represented  by  bundles  from  anterior  olfactory 
regions  (stria  medullaris,  seventh  week) ,  by  the  commissura  habenularis,  and  by 
bundles  to  caudal  regions  (fasciculus  retrofleocus  of  Meynert  to  the  inter  pedun- 
cular ganglion,  middle  of  second  month),  (pp.  467  and  505.)  The  posterior 
commissure  fibers  are  formed  early  in  the  second  month  in  the  fold  between 
mid-  and  inter-brain  (Fig.  467).  (Fig.  470). 


St. 


FIG.  470. — Construction  of  the  brain  of  a  19  mm.  human  embryo  (7^  weeks),  showing  the  stage  of 
development  of  some  of  the  principal  fiber-systems.  His. 

C.c.,  posterior  commissure;  F.  s.,  tractus  solitarius;  F.t.,  fasciculus  spinalis  trigemini  (spinal  V); 
K,  nuclei  of  dorsa!  funiculi  of  cord;  L.,  medial  longitudinal  fasciculus;  M.,  fasciculus  retro- 
flexus  of  Meynert;  Ma.,  mammillary  bundle;  «.*".,  nervus  intermedius;  O.,  olive;  Ol.,  olfactory 
nerve;  S.,  fillet;  St.,  stria  medullaris  thalami;  T.,  lhalamic  radiation;  T.  o.,  tractus  opticus; 
V,  Gasserian  ganglion;  VII,  facial  nerve  and  geniculate  ganglion;  VIII,  ganglia  of  acoustic 
nerve;  IX,  N.  glossopharyngeus;  X,  N.  vagus. 


The  Telencephalon  (Rhinencephalon,  Corpora  Striata  and  Pallium). 

To  understand  the  development  of  this  part  of  the  brain  it  is  necessary  to 
keep  firmly  in  mind  certain  relations  which  are  laid  down  at  a  comparatively 
early  stage.  Some  of  these  relations  are  shown  in  the  diagram  of  the  inner  sur- 
face of  a  model  of  a  brain  of  four  weeks.  At  this  stage  the  pallium  is  unpaired, 
i.e.,  there  is  no  median  furrow  separating  the  two  halves  of  the  pallial  expansion. 
The  various  boundaries  of  the  pallium  in  one  side  are  (i)  the  median  line  uniting 


THE  NERVOUS  SYSTEM. 


539 


the  two  halves  of  the  pallial  expansion  (Fig.  471,  be)]  (2)  the  boundary  line  or 
line  of  union  with  the  thalamus  lying  caudally  (pallio-thalamic  boundary) 
(Fig.  471,  cd}\  (3)  the  boundary  between  pallium  and  corpus  striatum  (strio- 
pallial  boundary)  (Fig.  471,  bd).  The  boundaries  of  the  future  corpus  striatum 
are  (i)  the  median  (Fig.  471,  ab),  (2)  the  strio-pallial  (Fig.  471,  bd),  (3)  the 
strkKhalamic  or  peduncular  (Fig.  471,  de)  and  (4)  the  strio-hypothalamic  (.  .rig. 
471,  ae).  The  internal  prominence  which  is  the  rudiment  of  the  coipus 
striatum,  has  three  limbs  or  crura,  (i)  a  ridge  proceeding  forward  (anterior 
crus),  which  corresponds  externally  to  the  furrow  (external  rhinal  furrow) 
fojming  the  lateral  boundary  of  the  anterior  olfactory  lobe,  (2)  a  middle  crus 


Prosencephalon 
(Fore  -brain) 


Rhinencepha 

Corpus  striatum 


Corpora  quadrigemioa 


Peduuculus  cerebrl 

Brachium  conjunctive 

and  velum  medullare 

aoterius 


Pars  optica  liypothalarai 
Pai-s  mamillaris  hypothalami    .. 
Pons  [Varolil 


Pars  ventralis  - 
Sulcus  limitans- 


(Lozenge- shaped 
•brain) 

Cerebellum 


FIG.  471.  —  From  a  model  of  the  brain  of  a  human  embryo  at  the  end  of  the  first  month,  right 
half,  seen  from  the  left.     His,  Spalteholz. 


corresponding  to  the  constriction  separating  the  two  olfactory  lobes,  and  (3)  a 
posterior  crus  corresponding  to  the  posterior  boundary  of  the  posterior  olfactory 
lobe.  This  latter  is  merged  with  the  earlier  furrow  separating  the  telencephalon 
from  the  thalamus  and  hypothalamus  (peduncular  furrow).  What  may  be 
called  the  main  body  of  the  corpus  striatum,  from  which  these  limbs  radiate, 
soon  becomes  expressed  externally  by  a  shallow  depression  in  the  lateral  sur- 
face of  the  hemispheres  immediately  dorsal  to  the  olfactory  lobes.  This 
depression  is  the  first  indication  of  the  /0ssa  Sylvii  (Fig.  465)  . 

The  boundaries  of  the  pallial  hemisphere  above  indicated  are  identical 
with  the  boundaries  of  the  future  /0r#w£W  0/M<wr0. 

The  median  lamina  uniting  the  two  halves  of  the  pallium  and  the  two  corpora 
striata  may  be  termed  the  lamina  terminates  and  represents  the  roof  plate  and 
floor  plate  of  this  region.  The  point  of  meeting  of  the  roof  plate  and  floor 


540 


TEXT-BOOK  OF  EMBRYOLOGY. 


plate  at  the  end  of  the  tube  is  often  taken  to  be  at  the  recessus  neuroporicus ; 
and  the  lamina  terminalis  or  end  wall  of  the  neural  tube,  more  strictly  speaking, 
is  limited  to  the  median  wall  ventral  to  this  point.  Here  it  will  be  understood 
as  including  the  median  wall  to  the  point  where  the  pallio-thalamic  boundary 
begins,  marked  later  by  the  angulus  prczthalamicus  of  His  (see  p.  547  and  Fig. 
480). 

Rhinencephalon. — The  term  rhinencephalon  is  a  convenient  one  for 
those  basal  structures  of  the  fore-brain  which  are  in  most  intimate  connection 
with  the  olfactory  nerve.  The  term  has  been  extended  by  some  to  include 
the  pallial  olfactory  structures.  For  descriptive  purposes  it  is  here  used  in 
the  more  limited  sense. 

At  the  fourth  week,  as  already  indicated  (p.  546,  Fig.  472) ,  there  is  a  slight  longi- 
tudinal furrow  on  the  external  surface,  marking  the  ventral  limit  of  the  pallial 


FIG.  472. — Lateral  view  of  outside  of  brain  shown  in  Fig.  471.     His. 

eminence.  The  part  of  the  brain  ventral  to  this  furrow  is  the  rhinencephalon, 
Somewhat  later  the  latter  becomes  better  marked  off,  the  fissure  forming  its 
boundary  on  the  lateral  surface  being  the  external  rhinal  fissure  (Fig.  462). 
Later  the  mesial  side  is  also  marked  off  by  an  extension  of  the  fissure  around 
on  the  mesial  side  (medial  rhinal  fissure)  and  also  by  a  notch,  the  incisura 
prima,  a  continuation  of  which  later  ascends  along  the  middle  part  of  the 
median  surface  of  the  hemispheres  and  is  known  as  the  anterior  arcuate  fissure 
(fissura  prima  of  His) .  (Fig.  480.)  The  existence  of  a  fissura  prima  in  early 
stages,  however,  is  doubtful.  At  about  this  time,  the  rhinencephalon  shows  a 
beginning  division  into  anterior  and  posterior  portions,  the  anterior  and  posterior 
olfactory  lobes,  the  whole  structure  assuming  a  bean-shape  (comp.  p.  542) 
(Fig.  465).  On  the  lateral  surface  immediately  above  this  constriction  is  the 
beginning  concavity  in  the  lateral  surface  of  the  hemispheres  which  marks  the 


THE  NERVOUS  SYSTEM. 


541 


earliest  appearance  of  the  fossa  Sylvii.  The  external  rhinal  fissure,  as  it 
becomes  more  pronounced,  may  be  regarded  as  an  extension  forward  of  the 
fossa  (anterior  crus  of  the  corpus  striatum) .  On  the  mesial  surface  the  incisura 
prima  marks  this  constriction.  With  the  further  curvature  of  the  hemispheres, 
ttn  anterior  lobe  becomes  bent  back  under  the  posterior  (third  month),  but 
lat?r  is  again  directed  forward.  It  contains  a  diverticulum  of  the  fore-brain 
cavity.  The  cavity  of  the  posterior  lobe  is  not  so  well  marked  off  anl  is 
bounded  by  the  corpus  striatum  and  the  inward  projection  of  the  incii.ura 
prima.  (Figs.  462,  463,  465,  466  and  480.) 

The  olfactory  nerve  at  the  end  of  five  weeks  has  reached  the  anterior  lobe 
on  its  ventral  and  posterior  side.  The  lobe  develops  into  the  receptive  center  5  for 
the  nerve — the  olfactory  bulb;  into  the  stalk  in  which  the  secondary  olfactory 


Gyms  olfact.  medialis 
Gyrus  olfact.  medius 


Gyrus  diagonalis     — -i 


Cerebellum 


Gyrus  ambiens 
Gyrus  semilunaris 


Olive 


FIG.  473. — Ventral  view  of  the  brain  of  human  foetus  at  the  beginning  of  the  4th  month.  Kollmann. 

tract  proceeds ;  and  also  into  a  triangular  area  where  the  tract  divides — the 
trigonum.  The  posterior  olfactory  lobe  develops  into  the  anterior  perforated 
space  and  an  eminence  known  as  the  lobus  pyriformis  which  becomes  reduced 
later  (comp.  Fig.  408,  G  and  H).  From  it  is  developed  the  gyms  olfactorius  later- 
alis,  connected  with  the  lateral  division  of  the  olfactory  tract  and  thegyri  ambiens 
and  semilunaris  (Fig.  473).  On  the  mesial  wall,  the  posterior  lobe  is  especially 
connected  with  the  region  between  the  anterior  arcuate  fissure  and  the  lamina 
terminalis  (trapezoid  area  of  His,  parolfactory  or  preterminal  area  of  G.  Elliot 
Smith)  (Fig.  480) .  Part  of  this  mesial  region  represents  the  anterior  portion 
of  the  archipallium  (comp.  Fig.  408,  G  and  H  and  p.  512). 

Corpora  Striata  and  Pallium. — The  leading  feature  of  the  development 
of  this  part  of  the  brain  is  the  great  expansion  of  the  pallial  hemispheres.  That 
part  of  the  brain  wall  marked  externally  by  the  fossa  Sylvii  and  internally  by  the 
body  of  the  corpus  striatum,  and  especially  that  part  where  the  corpus  striatum 


542  TEXT-BOOK  OF  EMBRYOLOGY. 

is  continuous  with  the  thalamus  (peduncular  part) ,  may  be  considered  as  a  fixed 
point  from  which  the  pallial  walls  expand  in  all  directions,  anteriorly,  dorsally 
and  posteriorly,  i.e.,  in  both  transverse  and  longitudinal  directions.  At  first, 
this  expansion  causes  the  pallial  hemispheres  to  assume  a  bean-shape  with  the 
hilum  at  the  fixed  point  (Fig.  465).  The  anterior  end  curves  downward  and 
forms  the  frontal  lobe  with  its  enclosed  cavity  (anterior  horn  of  the  lateral  ven- 
tricle). The  posterior  end  curves  downward  caudally  and  forms  the  temporal 
lobe  with  the  descending  horn  of  the  lateral  ventricle.  At  the  same  time,  owing 
to  the  great  expansion  in  a  transverse  plane  of  each  pallial  eminence,  the 
median  lamina  uniting  them  (Figs.  463  and  464)  not  sharing  in  this  growth, 
there  are  formed  the  hemispheres  with  their  cavities,  the  lateral  ventricles,  and 
the  great  longitudinal  fissure  between  the  hemispheres.  Later,  vascular 
mesodermal  tissue  fills  this  fissure,  forming  the  faloc  cerebri.  The  paired 
cavities  of  the  pallium  are  connected  with  the  unpaired  end-brain  cavity  (aula) 
by  the  foramina  of  Monro,  the  boundaries  of  which  are  the  same  as  those  of  the 
pallium  described  above  (p.  538). 

At  first  the  walls  of  the  telencephalon,  like  those  of  other  parts  of  the  tube, 
are  epithelial  in  character  and  nearly  uniform  in  thickness.  By  proliferation 
there  is  formed  a  several-layered  epithelium  differentiated  into  an  inner 
nuclear  layer  and  an  outer  marginal  layer.  Later  a  mantle  layer  is  differen- 
tiated. The  hemispheres  are  late  in  development  and  until  the  end  of  the 
second  month  the  walls  are  thin  and  simply  show  the  above  three  layers. 
Toward  the  end  of  the  first  month  a  greater  activity  in  cell  proliferation  takes 
place  in  the  basal  portion  of  the  telencephalon  which  thickens  into  the  corpus 
striatum.  At  eight  weeks  there  first  appears  on  the  external  surface  of  the 
corpus  striatum,  a  cortical  layer  of  cells  lying  next  the  marginal  layer  and  sepa- 
rated from  the  inner  layer  by  an  intermediate  layer  comparatively  free  of  cells 
and  known  as  the  fibrous  or  medullary  layer  (see  p.  554) .  The  differentiation 
thus  begun  extends  gradually  around  the  circumference  of  the  hemispheres 
until  the  mesial  surface  is  reached.  This  differentiation  permanently  ceases 
at  the  medial  pallial  margin.  The  cortical  layer  does  not  extend  as  far  as 
the  medullary  layer,  thus  leaving  an  uncovered  medullary  layer  on  the  mesial 
hemisphere  wall.  As  a  result  of  this,  there  is  in  this  region,  passing  toward 
the  median  line,  (i)  a  region  covered  with  a  cortical  layer  (limbus  cortical  is 
of  His);  (2)  an  uncovered  medullary  layer  (limbus  medullaris);  (3)  a  fibrous 
transitional  zone  (the  tcenia)  passing  into  (4)  a  membranous  zone,  the  roof 
plate. 

This  process  resembles  that  taking  place  in  other  parts  of  the  neural  tube, 
in  which  there  is  the  same  progressive  development  from  the  ventral  portion 
of  the  lateral  wall  to  the  dorsal  border  of  the  same,  where  the  latter  passes  into 
the  roof  plate  which  is  either  ependymal  or  expanded  into  a  thin  membrane. 


THE  NERVOUS  SYSTEM.  543 

The  longitudinal  growth  of  the  hemispheres  naturally  affects  the  form  of  a 
number  of  its  structures.  As  already  mentioned,  this  growth  consists  in  an 
elongation  around  a  fixed  point,  which  may  be  regarded  as  located  on  its  ven- 
tral border,  the  result  of  this  being  a  curving  down  in  front  and  behind  ihis 
point.  This  is  especially  marked  in  the  caudal  half  which  thereby  becones 
curled  first  ventrally  and  then  forward,  thus  forming  a  spiral.  This  growth  in 
length  is  interstitial,  i.  e.,  due  to  expansion  of  the  intermediate  parts,  and  fari 
passu  with  it  there  is  an  elongation  not  only  of  the  corpus  striatum  and 
structures  in  the  mesial  hemisphere  wall  (hippocampal  formation,  corpus  ca  llo- 
sum,  chorioid  plexus  of  lateral  ventricle),  but  also  of  adjacent  thalamic  struc- 
tures (stria  terminalis  or  semicircularis),  as  described  later. 


FIG.  474. — View  of  the  inside  of  the  lateral  wall  of  anterior  part  of  fore-brain.     Human  embryo 

of  about  4^  weeks.     His. 

C,  Corpus  striatum;  H,  pallium;  h.  R,  posterior  olfactory  lobe;  L,  lamina  terminalis;  O,  re- 
cessus  (prae-?)  opticus;  R.  i.,  recessus  infundibuli;  S.  M..  sulcus  hypothalamicus;  St,  hypo- 
thalamus;  T,  thalamus;  v.  R.,  anterior  olfactory  lobe. 

The  early  divisions  of  the  corpus  striatum  have  been  mentioned,  and  also 
the  relations  of  its  parts  with  the  rhinencephalon.  The  anterior  end  of  the 
corpus  striatum  at  this  period  and  later  shows  a  longitudinal  division  into 
three  portions,  a  lateral,  a  middle  and  a  medial,  due  to  the  original  division 
into  three  limbs  described  above  (p.  538).  (Figs.  474,  475,  and  476.)  With 
the  elongation  backward  of  the  hemisphere  the  corpus  striatum  also  becomes 
elongated,  being  drawn  out  and  curled  around  the  peduncle  or  stalk  of  the 
hemisphere  and  forming  a  thickening  along  the  elongated  wall.  This  caudal 
prolongation  of  the  striatum  is  its  cauda  (tail)  and  extends  to  the  tip  of  the  in- 
ferior horn  (Figs.  475  and  476).  The  medial  portion  of  the  corpus  striatum 
forms  a  triangular  projection  (Figs.  464  and  466)  the  edge  of  which  is  directed 
toward  the  foramen  of  Monro. 


544 


TEXT-BOOK  OF  EMBRYOLOGY. 


The   stalk   of  the  hemisphere  has  already  been  mentioned  as  including 
that  part  where  corpus  striatum  and  thalamus  meet.     In  this  region,  according 


v.Rl. 


FIG.  475. — View  of  inside  of  the  lateral  wall  of  lateral  ventricle  of  a  human  foetus  at  beginning 

of  third  month.     His. 

Bb,  bulbus  olfactorius;  C.L,  lateral  limb  of  corpus  striatum;  C.m.,  medial  segment  (consisting  of 
the  middle  and  inner  limbs)  of  the  corpus  striatum.  The  furrow  between  these  two  parts 
opens  into  the  anterior  olfactory  lobe;  hRl.,  posterior  olfactory  lobe;  L.f.,  frontal  lobe;  L.O., 
occipital  lobe;  Og.,  olfactory  nerve;  R.  i.,  recessus  infundibuli;  R.  <?.,  recessus  (prse-?)  opticus; 
St.,  stalk  of  hemisphere  (strio-thalamic  junction);  V.I.,  lateral  ventricle;  v.Rl.+Bb,  anterior 
olfactory  lobe. 

to  some,  there  is  a.  fusion  of  the  striatum,  the  medial  wall  of  the  hemisphere  and 
the  anterior  part  of  the  thalamus.     According  to  others,  the  increase  in  bulk  of 


Medial  wall 


Chorioid  plexus  of 
lateral  ventricle 


Lamina  terminalis 

Taenia  thalami 
Thalamus 

Habenula— 
Trigonum  subpineale 
Cerebellum 


Myelencephalon 


Lateral  ventricle 
:audate  nucleus  (head) 

Medial  wall 
Caudate  nucleus  (tail) 
Pineal  body 
Median  sulcus 


Mesencephalon 
Fourth  ventricle 


FIG.  476. — Dorsal  view  of  the  brain  of  a  3  months'  (45  mm.)  human  foetus.    The  dorsal  part  of  each 
cerebral  hemisphere  has  been  removed.     Kollmann. 

this  region  is  produced  by  a  simple  thickening  of  the  walls,  thus  causing  a  flat- 
tening out  or  shallowing  of  the  grooves  marking  the  junctions  of  striatum  and 


THE  NERVOUS  SYSTEM. 


545 


FIG.  477. — i,  2  and  3,  Schematic  horizontal  sections  through  human  embryonic  fore-brains  at  dif- 
ferent stages  of  development;  4,  vertical  section  through  fore-brain  at  about  same  stage  as  i. 
Goldstein. 

a,  That  part  of  the  lateral  ventricle  lying  between  the  corpus  striatum  and  the  junction  of  medial 
hemisphere  wall  and  thalamus  (leading  into  the  inferior  horn);  b,  furrow  or  trough  between 
mesial  hemisphere  wall  and  thalamus,  produced  by  backward  extension  of  hemisphere;  c.  i., 
internal  capsule;  P.M.,  foramen  of  Monro;  h,  external  surface  at  junction  of  mesial  hemi- 
sphere wall  and  thalamus;  Str.,  corpus  striatum;  Th.,  thalamus;  U,  place  where  mesial  hemi- 
sphere wall  continues  into  the  thalamus  wall  (junction  of  hemisphere  wall  and  thalamus); 
U1,  place  where  mesial  hemisphere  wall  is  continuous  with  lateral  hemisphere  wall. 

In  i,  owing  to  the  thickening  of  U  and  growth  of  the  corpus  striatum,  these  two  are  brought 
into  apposition,  as  indicated  by  the  dotted  lines  on  the  right,  and  apparently  fuse,  obliterating 
a  and  producing  the  condition  shown  in  2  and  3.  In  2  and  3  the  position  of  the  former 
space  a  is  indicated  by  the  dotted  lines  a — a'  By  comparison  with  4,  it  will  be  seen  that  this 
obliteration  by  apparent  fusion  is  actually  produced  by  a  filling  up  from  the  bottom  of  a  (in- 
dicated faintly  by  dotted  lines  on  the  right  in  4).  The  thickening  of  the  walls  at  this  region 
also  produces  a  shallowing  of  b  (indicated  by  dotted  lines  on  the  right  in  i).  The  principal 
cause  of  this  general  thickening  is  the  passage  of  the  fibers  of  the  thalamic  radiation  to  the 
hemispheres  and,  later,  of  fibers  from  hemisphere  to  pes,  forming  the  internal  capsule  (4,  2 
and  3). 


546 


TEXT-BOOK  OF  EMBRYOLOGY. 


thalamus  on  the  ventricular  surface,  and  between  medial  hemisphere  wall  and 
thalamus  externally  (Fig.  477).  The  effect  is  much  the  same  whether  accom 
plished  by  apposition  and  fusion  or  by  interstitial  thickening,  massive  con- 
nections being  formed  which  consist  mainly  of  fibers  connecting  hemispheres 
and  thalamus,  the  foramen  of  Monro  at  the  same  time  being  changed  in  form 
to  a  slit.  From  the  metathalamic  region  the  fibers  of  the  optic  and  acoustic 
pathways  grow  forward  into  the  hemispheres  (see  also  p.  537),  entering  more 
caudally  and  forming  the  retro-  and  sublenticular  portions  of  the  internal  capsule 
(comp.  p.  537).  That  part  of  the  thalamic  radiation  from  the  anterior  portion 
of  the  thalamus  (fillet  pathway)  also  forms  a  part  of  the  internal  capsule  as 
described  on  p.  537.  Later,  the  internal  capsule  is  completed  by  the  growth 


Medial  wall 


Caudate  nucleus 

Internal  capsule 

Lentiform  nucleus 

Lateral  wall 


Chiasma 
Recessus  infundibuli 


Chorioid  fissure 
Mesencephalon 

Pedunculus  cerebri 

Cerebellum 

Myelencephalon 


FIG.  478. — Lateral  view  of  the  brain  of  a  3  months'  (42  mm.)  human  foetus.     The  lateral  wall  of 
the  left  cerebral  hemisphere  has  been  removed.     His,  Kollmann. 

from  the  pallium  of  descending  fibers  from  the  neopallial  cortex,  through 
the  striatum  to  the  pes.  By  these  various  traversing  fibers  the  striatum  is 
divided  into  the  nucleus  lenticularis  or  lentiformis  and  the  nucleus  caudatus. 
The  posterior  arm  of  the  internal  capsule  is  formed  by  fibers  passing  between 
and  thus  separating  thalamus  and  lenticularis  (Figs.  477  and  478). 


THE  ARCHIPALLIUM. 

During  the  fifth  week,  following  the  stage  shown  in  Figs.  471  and  472, 
the  pallial  evaginations  or  hemispheres  have  become  much  more  pronounced 
and  consequently  the  foramina  of  Monro  much  better  defined.  A  comparison 
will  show  that  the  boundaries  of  the  foramen  of  Monro  are  essentially  unaltered. 
Anteriorly  it  is  bounded  by  the  medial  wall  connecting  the  two  hemispheres, 
posteriorly  by  the  boundary  between  pallium  and  thalamus,  ventrally  by  the 
corpus  striatum  and  junction  of  it  and  thalamus  (Figs.  463  and  479). 


THE  NERVOUS  SYSTEM. 


547 


At  the  beginning  of  the  sixth  week  the  foramen  of  Monro  has  changed  some- 
what in  shape.  The  pallio-thalamic  part  of  its  boundary  passes  forward  and 
forms  the  above-mentioned  (p.  540)  acute  angle  (angulus  praethalamicus)  with 
that  part  of  the  wall  uniting  the  two  hemispheres  (lamina  terminalis).  The 
latter  wall  descends  to  the  region  of  the  optic  recess.  The  inferior  part  of  the 
foramen  is  partly  closed  by  the  medial  part  of  the  corpus  striatum  as  already 
described.  (Comp.  Figs.  479,  464  and  466.)  In  the  ependymal  mesial  wall 
of  the  hemispheres  just  below  the  taenia,  described  above,  there  arises  a  folding 
inward,  which  begins  anteriorly  near  the  angulus  praethalamicus  and  proceeds 
caudally  along  the  upper  (pallio-thalamic)  border  of  the  foramen  of  Monro. 
This  infolding  is  the  chorioid  fissure.  In  the  ependymal  mesial  wall  there  are 


Pallium 


Foramen  of  Monro 
Corpus  striatum 


Eye 


III  ventricle 
Chorioid  fissure 


Mesodermal  tissue, 
forming  later  the 
chorioid  plexus. 


FIG.  479. — Transverse  section  through  fore-brain  of  a  i6mm.  embryo  (six  to  seven  weeks).     His* 

now  the  following :  limbus  chorioideus  (the  infolded  part)  and  a  small  strip  of  the 
ependyma  wall  below  the  fold,  the  lamina  infrachorioidea  (Fig.  480).  This 
imagination  soon  becomes  very  deep,  resulting  in  the  formation  of  a  double- 
layered  ependymal  fold  (the  chorioid  fold,  plica  chorioidea)  lying  in  the  lateral 
ventricle  over  the  corpus  striatum  (Figs.  479,  464  and  482).  Later,  vascular 
mesodermal  tissue  passes  in  from  the  falx  between  the  lips  of  this  fold  and 
thereby  forms  the  chorioid  plexus  of  the  lateral  ventricles.  The  chorioid  fissure 
is  at  first  quite  short,  but  becomes  elongated  (Fig.  481)  with  the  above-described 
posterior  elongation  of  the  hemisphere  of  which  it  is  a  part,  and  thus  extends 
into  the  inferior  horn  of  the  temporal  lobe.  (Figs.  481  and  482.) 

Toward  the  end  of  the  second  month,  according  to  some  authorities  (His), 
but  not  until  considerably  later,  according  to  others  (Hochstetter,  Goldstein), 
another  furrow  appears  in  the  limbus  corticalis  above  and  parallel  to  the  chori- 


548  TEXT-BOOK  OF  EMBRYOLOGY. 

oid  fissure,  and  known  as  the  posterior  arcuate  fissure.  This  fissure  does  not 
extend  at  first  as  far  forward  as  the  chorioid,  but  extends  farther  caudally, 
arching  downward  in  the  temporal  lobe  around  the  caudal  end  of  the  chorioid 
fissure  (Fig.  481).  The  posterior  arcuate  fissure  is  a  total  fissure,  involving  the 
whole  wall  and  producing  a  fold  on  the  inner  surface  of  the  medial  hemisphere 
wall  (plica  arcuata).  The  temporal  or  caudal  part  of  this  whole  formation 
persists  in  the  adult  without  much  further  change.  The  fissure  here  becomes 
the  hippocampal  fissure  separating  the  fascia  dentata  from  the  gyrus  hippocam- 
pus; the  part  rolled  in  by  the  hippocampal  fissure  produces  the  eminence  in 
the  lateral  ventricle  known  as  the  cornu  ammonis  or  hippocampus  major; 


FVW-* 


Vmr  Fstr  hRh 

FIG.  480. — Diagram  of  a  graphic  reconstruction  of  the  mesial  hemisphere  wall  of  a  16  mm.  human 
embryo  (about  six  weeks).  His,  Ziehen.  Cavities  are  dotted,  cut  surfaces  are  lined. 

Apt,  Angulus  praethalamicus;  Atr,  preterminal  area;  Fpr,  anterior  arcuate  fissure  (fissura  prima); 
Frhl,  mesial  termination  of  lateral  rhinal  fissure;  hRh,  posterior  olfactory  lobe  (tuberculum 
olfactorium  +  substantia  perforata  anterior);  Lt,  lamina  terminal's  (lined);  Vmr,  depression 
between  the  two  olfactory  lobes;  vRh,  anterior  olfactory  lobe  (bulbus  olfactorius  +  tractus 
olfactorius  +  trigonum  olfactorium). 

the  edge  of  the  limbus  corticalis  forms  the  fascia  dentata;  the  limbus  medullaris 
or  exposed  fibrous  part  is  thefimbria  which  is  continued  by  its  thinning  edge 
or  tania  fimbricB  into  the  ependymal  or  epithelial  portion  (lamina  chorioidea) 
of  the  chorioid  plexus  of  the  lateral  ventricle.  The  chorioid  plexus  is  attached 
by  the  taenia  chorioidea  and  lamina  infrachorioidea  (here  the  lamina  affixa)  to 
the  brain  wall,  usually  near  the  junction  of  corpus  striatum  and  thalamus, 
thereby  forming  a  part  of  the  wall  of  the  inferior  horn  of  the  lateral  ventricle. 
At  this  line  of  junction  of  thalamus  and  hemisphere  wall  is  formed  the  stria 
terminalis.  The  fimbria  is  continuous  anteriorly  with  the  posterior  pillar  of 
the  fornix.  (Fig.  482.) 

The  anterior  part  of  the  hippocampal  formation  above  described  undergoes 


THE  NERVOUS  SYSTEM. 

Corpus  callosum  Hippocampal  fissure 


549 


Olfactory  stalk 


. 

Lamina  terminalis     | 
Anterior  commissure 
Beginning  anterior  column  of  fornix 


Hippocampal  fissure 
horioid  fissure 


FIG.  481. — Graphic  reconstruction  of  the  mesial  hemisphere  wall  of  a  human  foetus 

(fourth  month).     His,  from  Quain's  Anatomy. 

C  and  v,  Anterior  and  posterior  parts  of  preterminal  area;  li,  lamina  infrachorioidea;  km,  limbus  or 
border  of  mesial  hemisphere  wall  (gyrus  dentatus  and  fimbria)  between  hippocampal  and 
chorioid  fissures;  P,  "stalk"  of  hemisphere. 


falx 


FIG.  482. — Diagram  of  a  transverse  section  through  the  fore-brain  of  a  human  foetus  (fourth 
month)  to  show  the  relations  of  the  margins  of  the  mesial  walls  of  the  hemispheres.  His, 
from  Quain's  Anatomy. 

Cs.,  corpus  striatum;  fi.t  limbus  medullaris  (fimbria);  fa.,  limbus  corticalis  (gyrus  dentatus);  h.f.t 
hippocampal  fissure;  Th.}  thalamus 


550 


TEXT-BOOK  OF  EMBRYOLOGY. 


further  modifications,  due  principally  to  the  development  of  commissural  fibers 
in  this  region.  Some  of  these  commissural  fibers  connect  the  representatives 
on  each  side  of  the  hippocampus  (limbus  corticalis)  of  this  region,  forming  the 
fornix  commissure,  but  most  of  them  (corpus  callosum)  connect  the  rest  of  the 
cortical  areas  (neopallial  areas)  of  the  two  hemispheres. 

There  are  two  views  regarding  the  formation  of  these  commissures.  Ac- 
cording to  one  view,  the  first  commissural  fibers  appear  in  the  upper  (dorsal) 
part  of  the  lamina  terminalis.  The  latter  subsequently  expands  pari  passu 


Corpus  callosum 
Fornix  (continuation  of  fimbria)    J 


Callosal  (continuation  of  hippocampal)  fissure 

i 


Olfactory  stalk  |      \      j 

Optic  commissure  (chiasma)        N^fe-fe.-. 

Lamina  terminalis  | 
Anterior  commissure 

Uncus 


Hippocampal  fissure 


FIG.  483. — Graphic  reconstruction  of  the  mesial  hemisphere  wall  of  a  120  mm.  foetus  (end  of  four 

months).     His,  from  Quain's  Anatomy. 
6,  Fimbria;  cs  ,  cavity  of  septum  pellucidum  ("fifth"  ventricle,  ventricle  of  Verga);  km,  limbus 

corticalis  (gyrus  dentatus);  P,  stalk  of  hemisphere;  v,  outline  of  cavity  of  hemisphere  (lateral 

ventricle) . 

with  the  expansion  of  the  corpus  callosum.  The  commissural  fibers  are  thus 
confined  to  the  original  walls  connecting  the  two  hemispheres.  According  to 
the  other  view,  there  is  a  secondary  fusion  of  the  mesial  hemisphere  walls  and 
in  these  fusions  the  fibers  cross.  The  first  fibers  appear  during  the  third  month 
and  form  at  first  a  small  band  in  the  upper  part  of  the  lamina  terminalis  (Fig. 
481).  These  fibers  come  partly  from  the  limbus  corticalis  (fornix  commissural 
fibers)  and  partly  from  other  parts  of  the  cortex  (callosal  fibers),  in  either  case 
traveling  along  the  intermediate  layer.  According  to  the  fusion  view,  the 
exposed  intermediate  layers  (limbi  medullares)  fuse  where  the  fibers  cross. 
This  fusion  can  easily  be  imagined  by  conceiving  the  opposite  surfaces  in 


THE  NERVOUS  SYSTEM. 


551 


question  to  be  brought  together  in  the  upper  part  of  Fig.  482.  It  is  more  prob- 
able, though,  that  not  only  the  first  fibers  cross  in  the  lamina  terminalis,  but 
that  the  later  ones  also  cross  in  extensions  of  the  latter.  There  are  three  views 
regarding  the  further  development  of  the  corpus  callosum.  The  first  is  that 
all  parts  are  represented  at  this  stage,  future  growth  being  by  intussusception  of 
fibers ;  the  second  is  that  the  part  first  formed  represents  the  genu,  the  rest  being 
added  caudally;  the  third  (His)  is  that  this  first  formed  part  represents  Ihe 
middle  portion  of  the  callosum,  both  anterior  (genu  and  rostrum)  and  posterior 
(splmium)  portions  being  subsequently  added  (Figs.  481  and  483).  This 
latter  view  is  indicated  in  Fig.  483,  the  later  additions  being  shaded  darker. 

As  the  callosal  fibers  connect  the  limbi  medullares,  the  limbus  corticalis 
anl  the  arcuate  fissure,  corresponding  to  the  gyrus  dentatus  and  hippocan  pal 
fissure  of  the  temporal  lobe,  lie  dorsal  to  the  callosum.  The  limbus  corticalis 
is  reduced  to  a  mere  vestige  (indusium  griseum  and  strice  Lancisi)  on  the 
dorsal  surface  of  the  corpus  callosum  the  fissure  becoming  the  callosal  fissure. 
The  part  of  the  limbus  medullaris  ventral  to  the  corpus  callosum,  corre- 
sponding to  the  fimbria  of  the  temporal  lobe,  forms  the  posterior  pillars  and 
body  of  the  fornix. 

These  relations  are  shown  in  the  following  table  from  His  (slightly  modi- 
fied): 


Upper  callosal  region 

Hippocampal  region 

Upper  lip  of  arcuate 

Gyrus  cinguli 

Gyrus  hippocampi 

fissure 

Arcuate  fissure 

Fissura  corporis   cal- 

Fissura  hippocampi 

Limbus  Corticalis 

losi 

Cortical  layer  of  low-    Cortical    covering  of 

Gvrus  dentatus 

er  lip    of    arcuate       callosum  (indusium 

fissure 

griseum  and  striae 

Lancisi) 

Limbus  Medullaris  < 

Medullary     part     of 
lower  lip 

Callosum  and  fornix 

Fimbria 

Taenia 

Taenia  fornicis 

Taenia  fimbriae 

Lamina  chorioidea 

Plica  chorioidea 

Plica  chorioidea 

Lamina      infrachorio- 

Lamina  affixa 

Taenia  chorioidea 

idea 

Fibers  from  the  hippocampus  enter  the  fimbria  and  pass  forward  in  the  pos- 
terior pillars  and  body  of  the  fornix.  In  or  near  the  lamina  terminalis  these 
fibers  of  the  fornix  descend,  forming  the  anterior  pillars  of  the  fornix,  and  thence 
pass  back  of  the  anterior  commissure  and  caudally  to  the  mammillary  region. 


552  TEXT-BOOK  OF  EMBRYOLOGY. 

They  are  joined  by  fibers  from  the  dorsal  surface  of  the  callosum  (fornix 
longus),  i.e.,  from  the  vestigial  hippocampal  formation,  many  of  which  also 
descend  in  front  of  the  anterior  commissure  to  the  rhinencephalon.  The  trian- 
gular mesial  area  (septum  pellucidum)  included  between  callosum  and  fornix 
probably  represents  an  extended  part  of  the  lamina  terminalis  or  "commis- 
sure-bed," in  which  a  cavity  is  formed,  the  so-called  fifth  ventricle  and  ventricle 
of  Verga.  A  remnant  of  the  hippocampal  formation  at  the  anterior  end  of 
the  callosum  is  represented  by  the  gyms  subcallosus  (Fig.  483). 

THE  NEOPALLIUM. 

The  hippocampal  or  cornu  ammonis  formation  and  preterminal  area 
represent  the  older  part  of  the  pallium  (archipallium)  comp.  pp.  468  and  469. 
This  part  of  the  pallium  is  olfactory  in  character,  being  mainly  a  higher  center 
for  the  reception  of  secondary  and  tertiary  olfactory  tracts.  In  its  extension 
backward  and  partial  obliteration  by  the  corpus  callosum,  its  embryologic 
presents  a  striking  similarity  to  its  phylogenetic  development  (compare  p.  468 ) 
The  rest  of  the  pallial  hemispheres  (neopallium)  are  occupied  by  the  non- 
olfactory  higher  centers. 

The  further  growth  of  the  neopallial  hemispheres  leads  to  their  extension 
backward,  overlapping  the  caudal  portions  of  the  brain  tube.  In  the  course 
of  this  extension  the  occipital  lobe  and  its  cavity,  the  posterior  horn  of  the  lateral 
ventricle,  are  formed.  The  growth  of  various  portions  of  the  hemisphere  sur- 
face is  unequal,  producing  folds  (convolutions)  and  fissures.  This  folding 
may  be  partly  due  to  growth  in  a  confined  space,  but  especially  important  is 
the  relation  between  gray  and  white  matter.  The  gray  matter,  containing  not 
only  fibers  but  also  neurone  bodies,  remains  spread  out  in  a  comparatively  thin 
layer,  probably  to  accommodate  associative  connections.  The  white  matter,  on 
the  other  hand,  increases  in  thickness.  This  leads  to  a  folding  of  the  outer 
layer.  The  position  of  these  folds  is  probably  partly  determined  by  the  local 
histological  differentiation  and  growth  of  various  cortical  areas  (p.  557). 
Only  some  of  the  earliest  and  most  important  of  these  folds  will  be  mentioned 
here. 

It  has  been  seen  (p.  539)  that  early  in  the  development  of  the  pallium  a 
shallow  depression  appears  on  the  external  lateral  surface  of  each  hemisphere, 
the  fossa  Sylvii  (Fig.  484).  The  bottom  of  this  is  the  future  insula.  It  is  ex- 
ternal to  the  corpus  striatum  and  does  not  grow  as  rapidly  as  the  parts  bound- 
ing it,  which  consequently  overlap  it,  forming  its  opercula.  These  bounding 
walls  are  formed  by  the  fronto-parietal  lobe  on  its  upper  side,  by  the  temporal 
on  its  lower,  and  by  the  orbital  on  its  anterior.  The  temporal  and  fronto- 
parietal  opercula  begin  about  the  end  of  the  fifth  month,  the  temporal  at  first 


THE  NERVOUS  SYSTEM. 


553 


growing  more  rapidly  but  later  the  fronto-parietal,  thereby  changing  the 
direction  of  the  Sylvian  fissure  from  an  oblique  to  the  more  horizontal  angle 
characteristic  of  man  as  compared  with  the  ape.  In  the  meanwhile  the 
development  of  the  frontal  lobe  leads  to  its  also  overlapping  the  insula.  If  the 


Parietal  lobe 


Occipital  lobe 


Mesencephalon 
Cerebellum 


Frontal  lobe 
Insula 

Bulbus  olfactorius 


Gyms  olfactor.  lat. 

Gyrus  semilunaris 
Gyms  ambiens 


FIG.  484. — Lateral  view  of  the  brain  of  a  human  foetus  at  the  beginning  of  the 
4th  month.     Kollmann. 

frontal  lobe  fully  develops,  it  forms  a  U-shaped  operculum  between  the  fronto- 
parietal  and  the  orbital,  if  it  does  not  so  fully  develop  it  forms  a  V-shaped 
operculum,  and  a  still  less  developed  condition  is  shown  by  a  Y-shaped  arrange- 
ment in  which  the  frontal  lobe  does  not  completely  separate  the  fronto-parietal 


Corpus  callosum 
Gyrus  cinguli  | 

I 


Sulcus  corp.  callosi 
I         Splenium 

|,          Fissura  parieto-occip. 


Cavum  septi  pellucidi  — 
Lamina  rostralis  — 
Area  parolfactoria  — ^ 
(praeterminalis) 


Cuneus 


Fissura  calcarina 


N.  olfact.      |      |      Fiss.  rhinica 
N.  optic.     Lob.  temp. 

FIG.  485. — Median  view  of  the  left  half  of  the  brain  of  a  human  foetus  at  the  end 
of  the  7th  month.     Kollmann. 

and  orbital  opercula.  The  opercula  cover  the  fore-part  of  the  Sylvian  fossa 
during  the  first  year.  Conditions  of  arrested  development  are  thus  indicated  by 
the  Y-shaped  anterior  ascending  branch  of  the  Sylvian  fissure  coupled  with  an 
absence  of  the  pars  triangularis  and  also  by  a  partial  exposure  of  the  island 


554  TEXT-BOOK  OF  EMBRYOLOGY. 

of  Reil.  In  the  ape  the  frontal  operculum  is  absent  and  the  island  of  Reil 
partly  exposed. 

Toward  the  end  of  the  third  month  the  calcarine  fissure  appears,  producing 
on  the  ventricular  surface  the  eminence  known  as  the  calcar  avis.  At  the 
beginning  of  the  fourth  month  the  parieto-occipital  fissure  unites  with  it  forming 
the  cuneus.  The  parieto-occipital  reaches  the  superior  border  of  the  hemi- 
spheres by  the  sixth  or  seventh  month.  At  the  sixth  month  the  fissure  of  Rolando 
(central  fissure)  appears.  The  condition  of  the  surface  of  the  hemisphere  at 
the  end  of  the  seventh  month  is  shown  in  Figs.  485  to  488. 

The  early  histogenetic  development  of  the  pallial  wall,  resulting  in  the  dif- 
ferentiation into  the  usual  ependymal,  mantle  and  marginal  layers,  has  been 
mentioned.  (Fig.  489).  The  next  stage,  already  alluded  to  (p.  549),  marks  a 


Gyrus  front,  med.  •— — ^fl|  §  SrV 

Mj*      }          \      .,    — ^B m  Sulcus  front,  sup. 

Gyrus  front,  inf.  — — ^lH  f  v*-| 

JP*  I  *•    L_^ Sulcus  front,  inf. 

Gyrus  front,  sup.  — 4   — gp*^        I  .  \& 

4  V^iHH—  Sulcus  praecentralis 

Gyrus     praecent.  -  "jjaUr--  *  , 

^*****t^       £  Jf        J    Sulcus  centralis 

*--;£  '•%        s        +.'-?**''     ^H_  Snlcus  postcentralis 

Lobulus  par.  sup.  -fll      -  m 

V'-v  .£  yT~_/_  Sulcus  interparietalis 

Lobulus  par.  inf.  — ^H  •*? 

V      'f^tldJft^HJIr; ''''  s/         Fissura  parieto-occipit. 
Lobus  occipitalis  3^^^^^      ^^^^^^ 

FIG.  486. — Dorsal  view  of  the  cerebral  hemispheres  of  a  human  foetus  at  the  end 
of  the  yth  month.     Kollmann. 

difference  in  development  between  the  pallium,  as  well  as  other  supraseg- 
mental  structures,  and  the  rest  of  the  walls  of  the  neural  tube.  This  stage 
consists  apparently  in  a  further  migration  outward  of  the  neuroblasts  and  their 
accumulation  under  the  marginal  layer,  forming,  at  eight  weeks,  a  definite 
layer  of  closely  packed  cells,  the  beginning  of  the  cortex  (Fig.  490).  Later 
neuroblast  migrations  probably  add  to  this  layer.  It  has  already  been  men- 
tioned that  the  fibers  of  the  thalamic  radiation  appear  in  the  pallial  walls  about 
this  time.  They  proceed  internally  to  the  cortical  layer  and  thus  mark  the 
beginning  of  the  fiber  layer  (medullary  layer)  which  by  later  myelination 
becomes  the  white  matter  of  the  hemispheres. 

The  extension  of  the  process  of  differentiation  of  the  cortical  layer  from  the 
region  of  the  corpus  striatum  over  the  rest  of  the  pallium  has  also  been  men- 
tioned (p.  542).  It  is  probable  that  the  afferent  pallial  fibers  (thalamic  radia- 
tion) in  their  growth  keep  pace  with  this  process.  Those  fibers  from  the  lateral 


THE  NERVOUS  SYSTEM. 


555 


geniculate  bodies  proceed  to  the  occipital  region,  those  from  the  medial  genicu- 
late  bodies  to  the  temporal,  and  those  from  the  ventro-lateral  thalamic  nuclei 
(continuation  of  the  medial,  fillet)  to  the  future  postcentral  region.  The 
afferent  pallial  fibers  are  often  termed  the  afferent  or  ascending  projection  fibers. 


Sulcus  postcentralis 


Sulcus  centralis 


Lobus  parietal,  sup. 

Region  of  gyrus  sup- 

ramarg.  and  angular. 

Ramus  post. 


Sulcus  tempor.  med. 

Post,  pole 
of  cerebrum 


Sulcus  front,  inf. 

Ramus  ant.  asc-. 
Fissura  Sylvii 


Lobus  temporalis 


Gyrus  temp.  sup.        Gyrus  temp.  med. 


FIG.  487. — Lateral  view  of  the  right  cerebral  hemisphere  of  a  human  fcetus  at  the  end 
of  the  yth  month.     Kollmann. 

The  axones  of  the  neuroblasts  of  the  cortical  layer  grow  inward,  entering  the 
medullary  layer.  Their  peripherally  directed  processes  become  the  apical 
dendrites  of  the  pyramid  cells  into  which  most  of  the  cortical  cells  differentiate. 
According  to  Mall  and  Paton,  this  change  of  direction  in  the  growth  of  the  axone 
is  due  to  a  turning  of  the  cell  axis  during  its  outward  migration.  It  would  seem 


Sulcus  orbitalis 


Insula 
Gyrus  olf.  lat. 

Gyrus  semilun. 

Gyrus  ambiens 
Pyramid 
Medulla 


Sulcus  olfactorius 
Lobus  olfactorius 


Post,  pole  of  cerebrum 


FIG.  488. — Ventral  view  of  the  brain  of  a  human  foetus  at  the  beginning 
of  the  sixth  month.     Retzius,  Kollmann. 

more  probable  that  the  cells  retain  an  original  bipolar  character  and  that  the 
inner  processes  differentiate  into  axones  instead  of  the  cells  going  through  a 
monopolar  stage  (pp.  484  and  485  and  Figs.  424  and  425).  The  axones  of  the 
cortical  cells  form  either  efferent  or  descending  projection  fibers,  proceeding  to 


556 


TEXT-BOOK  OF  EMBRYOLOGY. 


other  parts  of  the  nervous  system,  or  crossed  (callosal)  and  uncrossed  association 
fibers,  connecting  various  cortical  areas  of  the  hemispheres.  The  basilar 
dendritic  processes  of  the  pyramid  cells  and  the  axone  collaterals  develop  last. 
Many  details  of  development  of  the  cells  in  Mammals  are  not  completed  until 
after  birth  (Fig.  491). 


m 


IrK'S 


..  .t 

Ml 


FIG.  489. 


FIG.  490 


FIG.  489. — Section  through  the  pallial  wall  of  a  two  months'  human  foetus.     His,  Cayal. 
a,  Layer  of  germinal  cells;  b,  nuclear  layer;  c,  mantle  layer;  d,  marginal  layer;  e,  germinal  cell 

FIG.  490. — Section  through  the  pallial  wall  of  a  human  foetus  at  the  beginning  of 

the  third  month.     His,  Cajal. 

a,  Layer  containing  germinal  cells;  b,  fibrous  (medullary)  layer  (rudimentary  white  matter);  c,  layer 
of  neuroblasts  forming  rudimentary  cortical  gray  matter;  d,  marginal  layer  (future  molecular 
layer);  e,  germinal  cell;  /,  g,  neuroblasts  with  radial  processes.  Spongioblasts  and  myelo- 
spongium  are  shown  on  the  right  side. 

During  the  fourth  and  fifth  foetal  months  the  cortical  layer  shows  a  differen- 
tiation into  a  denser  outer  and  an  inner  layer.  During  the  sixth  and  seventh 
months  a  differentiation  and  grouping  of  the  nerve  cells  begins  which  results 
in  the  formation  of  six  cortical  layers  (Brodmann).  These  are:  (i)  the  zonal 


THE  NERVOUS  SYSTEM. 


557 


layer  (marginal  layer,  molecular  layer  of  adult),  (2)  the  external  granular  layer 
(layer  of  small  pyramid  cells  of  adult),  (3)  pyramid  layer  (medium  and  large 
pyramid  cells),  (4)  internal  granular  layer,  (5)  ganglionic  layer  (internal  pyra- 
mid cells) ,  (6)  multiform  layer  (polymorphous  cells) .  By  various  local  modifi- 
cations of  this  six-layered  cortex  the  differentiation  of  the  various  histological 
areas  of  the  adult  cortex  is  brought  about.  In  the  calcarine  region  of  the 
occipital  lobe,  in  the  sixth  month,  the  internal  granular  layer  differentiates  into 


FIG.  491.  —  Section  through  cortex  of  a  mouse  foetus  before  birth,  showing  later  stages  of 

differentiation  of  pyramid  cells.     Golgi  method.     Cajal. 

a,  large  pyramid  cells;  b,  c.  medium-sized  and  small  pyramid  cells;  d,  beginning  collaterals  of,  e, 
axis-cylinders  or  axones;  /,  horizontal  cell  of  molecular  layer.  Basal  dendrites  of  pyramid 
cells  are  beginning  to  appear. 


two  layers  between  which  is  formed  the  line  of  Gennari  which  contains  termi- 
nations of  the  fibers  from  the  lateral  geniculate  bodies,  representing  the  visual 
pathway.  This  area  is  the  visual  cortex.  In  the  temporal  (future  transverse 
gyri)  and  postcentral  regions,  areas  are  differentiated  which  mark  the  re- 
ception of  the  terminations  of  the  fibers  of  the  acoustic  and  somaesthetic 
(medial  fillet)  pathways.  These  areas  are  thus,  respectively,  the  auditory  cortex 
and  the  somasthetic  (general  bodily  sensation)  cortex.  (Cf.  Fig.  409.) 

In  the  precentral  region,  the  internal  granular  layer  becomes  merged  with 


558  TEXT-BOOK  OF  EMBRYOLOGY. 

the  adjoining  layers  and  practically  disappears,  the  two  inner  layers  become 
more  or  less  fused  and  in  them  certain  cells  develop  to  a  great  size  forming  the 
layer  of  giant  pyramid  cells.  It  is  the  axones  of  these  cells,  in  all  probability, 
which  proceed  as  the  pyramidal  tracts  through  the  middle  part  of  the  internal 
capsule  and  pes  to  the  epichordal  segmental  brain  and  cord.  The  area  in 
which  these  cells  lie  is  the  motor  cortex  (cf .  Fig.  409) .  Descending  axones  de- 
velop similarly  from  cells  in  the  calcarine  area,  possibly  here  also  from  large 
pyramidal  cells  of  the  fifth  and  sixth  layers  (solitary  cells  of  Meynert),  which 
probably  pass  to  the  anterior  colliculus  (operating  there  upon  reflex  eye 
mechanisms). 

In  the  whole  pallium  there  are  thus  four  great  projection  fields,  differen- 
tiated both  by  their  histological  structure  and  their  connections.  These  are  (i) 
the  archipallial  olfactory  area  with  mesial  ascending  and  descending  connections ; 
(2)  the  visual;  (3)  the  acoustic;  (4)  the  somatic.  The  systems  of  projection  fibers 
of  the  three  neopallial  fields  are  lateral.  The  visual  and  acoustic  fields  repre- 
sent certain  specialized  and  concentrated  groups  of  receptors  (rods  and  cones, 
hair  cells  of  organ  of  Corti)  upon  which  stimuli  of  a  certain  definite  nature 
(light  and  sound  waves),  from  distant  objects,  are  focussed  by  means  of  acces- 
sory apparatus  (eye,  ear).  The  somatic  area  represents  receptors  scattered 
over  the  whole  organism.  In  the  visual  and  acoustic  mechanisms,  the  efferent 
element  is  small  or  lacking  in  both  peripheral  apparatus  and  cortical  areas,  in  the 
somatic  the  efferent  element  is  large  and  is  represented  cortically  by  an  area 
(motor,  precentral  area)  distinct  from  that  of  the  receptive  portion  (somaes- 
thetic,  postcentral  area).  Gustatory  and  other  visceral  areas  have  not  been 
well  determined  (vicinity  of  archipallium  ?) . 

These  four  primary  sensori-motor  fields  are  probably  the  first  differentiated 
of  the  various  pallial  cortical  areas.  This  is  evidenced  by  the  myelination 
(comp.  p.  494)  which  first  involves  the  projection  fibers  of  these  areas  (at  or 
soon  after  birth,  Flechsig),  the  afferent  projection  fibers  probably  myelinating 
before  the  efferent  (Figs.  492  and  493). 

The  process  of  myelination  next  spreads  over  areas  adjoining  the  primary 
areas,  the  intermediate  areas  of  Flechsig.  Descending  projection  fibers  from 
these  areas  in  the  frontal,  temporal  and  occipital  lobes  are  probably  represented 
by  the  cortico-pontile  systems  of  fibers,  securing  cerebellar  regulation  of  pallial 
reactions.  The  presence  of  other  fibers  connecting  with  thalamic  nuclei 
is  probable,  but  knowledge  of  their  develoDment  and  connections  is  very 
incomplete. 

The  cells  whose  axones  form  descending  or  efferent  projection  fibers  con- 
stitute only  a  small  fraction  of  the  cortical  cells.  The  great  majority  are  asso- 
ciation cells  whose  axones,  or  collaterals,  pass  across  the  median  line  in  the 
lamina  terminalis  as  the  callosal  fibers  already  mentioned  (p.  550)  or  pass 


THE  NERVOUS  SYSTEM. 


559 


to  distant  or  near  parts  of  the  same  hemisphere.  In  general,  these  develop  later 
than  the  projection  neurones  and  the  completion  of  their  development  is  carried 
to  a  much  later  period.  Variations  which  arise  in  their  differentiation  and  ar- 
rangement probably  contribute  largely  to  the  formation  of  various  histological 
areas  which  develop  at  different  periods.  These  local  inequalities  of  growth 
probably  constitute  a  factor  in  the  production  of  the  convolutions  appearing 
later  than  those  already  mentioned  in  connection  with  the  primary  areas.  The 
last  areas  to  myelinate,  the  terminal  areas  of  Flechsig,  are  poor  in  projection 
fibers  and  are  thus  composed  largely  (entirely  ?,  Flechsig)  of  association  cells. 
It  is  the  extent  of  these  last  developing  areas  which  constitutes  the  principal 
difference  between  the  human  cortex  and  that  of  related  forms.  These  pallial 


B 


FIG.  492. — Diagram  of  cortical  areas  of  mesial  surface  of  pallium  as  determined  by  the  myelogenetic 
method      Flechsig,  from  Quain's  Anatomy.     For  explanation  see  Fig.  493. 


areas  are  those  which  continue  to  grow  in  human  development.  Myelination 
in  the  cortical  areas  may  continue  for  twenty  years  or  so.  It  is  a  significant 
fact  that  the  last  areas  to  develop  are  comparatively  poor,  even  when  completely 
developed,  in  both  cells  and  fibers  (Campbell).  The  association  neurones 
thus  probably  follow  the  same  order  of  development  as  the  projection  systems. 
As  their  development  spreads  from  the  primary  receptive  areas  (perceptions  ?) , 
the  incoming  stimuli  receive  a  more  and  more  extended  associative  " setting" 
(psychologically,  the  "meaning"  or  "significance"  of  perceptions?),  extensive 
associations  between  the  various  areas  being  provided  by  the  extension  of  their 
development  to  the  terminal  areas  (rendering  possible  the  association  of 
symbols:  mental  processes?). 


560 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  general  biological  significance  of  this  late  development  of  the  pallium 
and  especially  of  its  associative  mechanisms  has  already  been  alluded  to. 
These  "added"  parts  of  the  nervous  system  are  the  most  modifiable  mechan- 
isms of  the  human  organism;  they  are  those  mechanisms  which  perform  its 
newest  and  most  highly  adaptive  adjustments.  The  other  parts  of  the  ner- 
vous system  are  fixed  at  birth,  but  the  cerebral  hemispheres  are  still  plastic 
for  the  reception  and  recording  of  individual  experience.  Such  experience 
symbolized  and  formulated  (spoken,  written,  etc.)  is  transmitted  to  the  next 
generation,  as  already  pointed  out  (p.  470).  An  example  of  the  far-reaching 
consequences  of  this  capacity  of  the  pallium  is  the  prolonged  period  of  infancy 
and  education  of  man. 


FIG.  493. — Diagram  of  cortical  areas  of  lateral  surface  of  pallium  as  determined  by  the  myelogenetic 

'method.     Flechsig,  from  Quain's  Anatomy. 
The  numerals  indicate,  in  a  general  way.  the  order  of  myelination.     The  primary  areas  (i-io)  are 

indicated  by  dots,  the  intermediate  areas  (11-31)  by  oblique  lines  and  the  terminal  or  final 

areas  (32-36)  by  clear  spaces. 

Anomalies. 

Those  anomalies  of  the  nervous  system  involving  more  general  develop- 
mental anomalies  (cyclopia,  anencephaly,  cranioschisis,  spina  bifida,  etc.)  are 
dealt  with  in  the  chapter  on  Teratogenesis  (XIX) .  Owing  to  the  fact  that  the 
nervous  system  consists  of  parts  which  are  more  or  less  separated,  and  yet  con- 
nected and  interdependent,  it  is  in  certain  respects  affected  differently  from  the 
other  organs  when  portions  of  it  are  injured  or  inhibited  in  development.  Thus 
an  injury  or  inhibition  in  development  of  one  part  of  the  nervous  system  may, 
because  of  the  dependence  upon  this  part  of  other  perhaps  distant  parts,  affect 
the  development  of  the  latter.  Even  in  the  adult,  injury  of  an  axone  leads  to  the 


THE  NERVOUS  SYSTEM.  561 

disappearance  of  that  portion  of  the  axone  distal  to  the  point  of  injury;  it  may 
also  lead  to  the  disappearance  of  the  entire  neurone  where  regeneration  is  not 
possible.  Such  an  injury  during  development  will  not  only  cause  a  disappear- 
ance of  the  whole  neurone,  but  it  may  also  lead  to  the  disappearance  of  other 
neurones  forming  links  in  the  same  functional  pathway.  Thus  a  develop- 
mental defect  involving  the  central  area  will  not  only  lead  to  absence  of  the 
pyramidal  tract,  but  also  to  partial  atrophy  of  the  corresponding  fillet  bundles. 
When  one  cerebellar  hemisphere  fails  to  develop,  there  results  a  correlated 
defect  in  its  centripetal  and  centrifugal  pathways.  The  opposite  inferior  olive 
is  practically  absent,  as  is  also  the  central  tegmental  tract  leading  to  that  olive. 
The  pontile  nuclei  of  the  opposite  side,  the  middle  peduncle  leading  from  them 
to  the  affected  cerebellar  hemisphere,  and  the  fibers  in  the  pes  which  pass  to 
the  pontile  nuclei  in  question  are  likewise  suppressed,  and  the  superior 
peduncle  and  red  nucleus  are  absent  or  reduced.  In  this  case  it  is  evident  that 
the  correlated  atrophy  affects  at  least  two  neurones  in  the  pathways  leading  to 
and  from  the  cerebellum.  This  illustrates  the  far-reaching  character  of  cor- 
related developmental  defects  in  the  nervous  system  arising  from  the  nature 
of  the  connections  between  various  portions  of  the  system. 

References  for  Further  Study. 

BARDEEN,  C.  R.:  The  Growth  and  Histogenesis  of  the  Cerebrospinal  Nerves  in  Mam- 
mals. Am.  Jour,  of  Anat.,  Vol.  II,  No.  2,  1903. 

DEJERINE,  J.:    Anatomic  des  centres  nerveux.     Tome  I,  Ch.  2  and  3. 

EDINGER,  L.:    Vorlesungen  iiber  den  Bau  der  nervosen  Zentralorgane.     Seventh  Ed. 

EDINGER,  L.  The  Relations  of  Comparative  Anatomy  to  Comparative  Psychology. 
Jour.  ofComp.  N enrol,  and  Psychol.,  Vol.  XVIII,  No.  5,  Nov.,  1908. 

FLECHSIG,  P. :  Einige  Bemerkungen  iiber  die  Untersuchungsmethoden  der  Grosshirnrinde 
insbesondere  des  Menschen.  Berichten  der  math.-phys.  Klasse  d.  Konigl. -Sachs.  Gesellsch.  d, 
Wissensch.  zu  Leipzig.  1904.  See  also  Johns  Hopkins  Hosp.  Bull.,  Vol.  XVI,  1905,  pp 

45-49- 

HARDESTY,  L:    On  the  Development  and  Nature  of  the  Neuroglia.     Am.  Jour,  of  Anat. t 

Vol.  Ill,  No.  3,  July,  1904. 

HARRISON,  R.  G.:  Further  Experiments  on  the  Development  of  Peripheral  Nerves. 
Am.  Jour,  of  Anat.,  Vol.  V,  No.  2,  May,  1906. 

HARRISON,  R.  G.:  Observations  on  the  Living  Developing  Nerve  Fiber.  Anat.  Record. 
Vol.  I,  No.  5,  1907. 

HARRISON,  R.  G.:  Embryonic  Transplantation  and  Development  of  the  Nervous 
System.  Anat.  Record,  Vol.  II,  No.  9,  1908. 

HERRICK,  C.  J.:  The  Morphological  Subdivision  of  the  Brain.  Jour,  of  Comp.  Neurol. 
and  Psychol.,  Vol.  XVIII,  No.  4,  1908. 

His,  W.:  Zur  Geschichte  des  menschlichen  Riickenmarkes  und  der  Nervenwurzeln. 
Abhandl.  der  math.-phys.  Klasse  der  Konig. -Sachs.  Gesellsch.  d.  Wissensch.,  Bd.  XIII,  1887. 

His,  W.:  Zur  Geschichte  des  Gehirns,  sowie  der  centralen  und  peripherischen  Nerven- 
bahnen  beim  menschlichen  Embryo.  Abhandl.  d.  math.-phys.  Klasse  d.  Konig.-Sachs. 
Gesellsch.  d.  Wissensch.,  Bd.  XIV,  1888. 


562  TEXT-BOOK  OF  EMBRYOLOGY. 

His,  W.:  Die  Neuroblasten  und  deren  Entstehung  im  embryonalen  Mark.  Abhandl.  d. 
math.-phys.  Klasse  d.  Konig.-Sachs.  d.  Wissensch.,  Bd.  XV,  1890.  Also  Arch.  f.  Anat.  u. 
Physiol.,  Anat.  Abth.,  1889. 

His,  W.:  Ueber  die  Entwickelung  des  Riechlappens  und  des  Riechganglions  und  iiber 
diejenige  des  verlangerten  Markes.  Verhandl.  d.  Anat.  Gesellsch.  zu  Berlin,  1889.  Also 
Abhandl.  d.  math.-phys.  Klasse  d.  Konig.-Sachs.  Gesellsch.  d.  Wissensch.,  Bd.  XV,  1889. 

His,  W.:  Die  Entwickelung  des  menschlichen  Rautenhirns  vom  Ende  des ersten  bis  zum 
Beginn  des  dritten  Monats.  I.  verlangertesMark.  Abhandl.  d.  math.-phys.  Klasse  d.  Konig.- 
Sachs.  Gesellsch.  d.  Wissensch.,  Bd.  XVII,  1891. 

His,  W.:  Die  Entwickelung  des  menschlichen  Gehirns  wahrend  der  ersten  Monate. 
Leipzig,  1904. 

JOHNSTON,  J.  B.:  The  Nervous  System  of  Vertebrates.     1906. 

KOLLMANN,  J.:  Handatlas  der  Entwickelungsgeschichte  des  Menschen.     Bd.  II,  1907. 

VON  KUPFFER,  K. :  Die  Morphogenie  des  Centralnervensystems.  In  Hertwig  's  Handbuch 
d.  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere.  Bd.  II,  Teil  III,  Kap.  8, 
1905. 

MARBURG,  O.:  Mikroskopisch-topographischer  Atlas  des  menschlichen  Zentralnerven- 
sy  stems,  1904, 

MEYER,  A.:  Critical  Review  of  the  Data  and  General  Methods  and  Deductions  of 
Modern  Neurology.  Jour.  o/Comp.  N enrol.,  Vol.  VIII,  Nos.  3  and  4,  1898. 

NEUMAYER,  L.:  Histo-  und  Morphogenese  des  peripheren  Nervensystems,  der  Spinal- 
ganglien  und  des  Nervus  sympathicus.  In  Hertwig's  Handbuch  der  vergleich.  und  experi- 
ment. Entwickelungslehre  der  Wirbeltiere,  Bd.  II,  Teil  III,  Kap.  10,  1906. 

RAMON  Y  CAJAL,  S. :  Sur  Porigine  et  les  ramifications  des  fibres  nerveuses  de  la  moelle 
embryonnaire.  Anat.  Anz.,  Bd.  V,  Nos.  3  and  4,  1890. 

RAMON  Y  CAJAL,  S. :  A  quelle  epoque  apparaissent  les  expansions  des  cellules  nerveuses 
de  la  moelle  epiniere  du  poulet?  Anat.  Anz.,  Bd.  V,  Nos.  21  and  22,  1890. 

RAMON  Y  CAJAL,  S.:  Textura  del  sistema  nervioso  del  hombre  y  de  los  vertebrados. 
Madrid,  1899-1904.  Also  translation  into  French  by  Azoulay,  1910-11. 

RAMON  Y  CAJAL,  S.:  Nouvelles  observations  sur  1'evolution  des  neuroblasts,  avec  quel- 
ques  remarques  sur  Phypothese  neurogenetique  de  Hensen-Held.  Anat.  Anz.,  Bd.  XXXII, 
Nos.  i,  2,  3  and  4,  1908. 

SCHAPER,  A.:  Die  morphologische  und  histologische  Entwickelung  des  Kleinhirns  der 
Teleostier.  Morph.  Jahrbuch,  Bd.  XXI,  1894. 

SCHAPER,  A.:  Die  friihesten  Differenzierungsvorgange  im  Centralnervensystems.  Arch. 
f.  Entw.-Mechan.,  Bd.  V,  1897. 

SMITH,  G.  E.:  On  the  Morphology  of  the  Cerebral  Commissures  in  the  Vertebrata,  etc. 
Trans.  Linncean  Soc.  of  London,  2d  Ser.  Zoology,  Vol.  VIII,  Part  12,  1903.  See  also  articles 
by  same  author  in  Jour,  of  Anat.  and  Physiol. 

STREETER,  G.  L.:  The  Development  of  the  Cranial  and  Spinal  Nerves  in  the  Occipital 
Region  of  the  Human  Embryo.  Am.  Jour,  of  Anat.,  Vol.  IV,  No.  i,  1904. 

STREETER,  G.  L. :  The  Peripheral  Nervous  System  in  the  Human  Embryo  at  the  End 
of  the  First  Month.  Am.  Jour,  of  Anat.,  Vol.  VIII,  No.  3. 

ZIEHEN,  TH.  :  Die  Morphogenie  des  Centralnervensystems  der  Saugetiere.  In  Hertwig's 
Handbuch  der  vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere.  Bd.  II5  Teil  III, 
Kap.  8,  1905. 

ZIEHEN,  TH.:  Die  Histogenese  von  Him-  und  Riickenmark.  Entwickelung  der 
Leitungsbahnen  und  der  Nervenkerne  bei  den  Wirbeltierer.  In  Hertwig's  Handbuch  def 
vergleich.  u.  experiment  Entwickelungslehre  der  Wirbeltiere,  Bd.  II,  Teil  III,  Kap.  IX,  1905, 


CHAPTER  XVIII. 

THE  ORGANS  OF  SPECIAL  SENSE. 
THE  EYE. 

The  receptive  mechanisms  of  all  the  general  and  special  sense  organs 
are  derived  from  the  ectoderm.  With  the  single  exception  of  the  eye,  all 
develop  as  direct  specializations  of  the  ectoderm  in  the  form  of  the  various 
neuro-epithelia.  The  eye  is  peculiar  among  the  sense  organs  in  that  its  recep- 
tive cells  are  not  derived  directly  from  surface  ectoderm,  but  only  indirectly  from 
the  ectoderm  after  it  has  become  folded  in  to  form  the  neural  canal.  The 
neuro-epithelium  of  the  eye  develops  as  a  direct  outgrowth  from  the  central 
nervous  system.  The  retina  is  a  modified  part  of  the  brain;  the  optic  nerves 
correspond  to  central  nervous  system  fiber  tracts.  Of  the  accessory  optic 
structures,  the  lens,  the  epithelium  of  the  lids  and  conjunctiva,  the  eyelashes, 
the  Meibomian  glands  and  the  epithelium  of  the  lacrymal  apparatus  are  of 
ectodermic  origin;  the  coats  of  the  eye,  the  sclera  and  chorioid,  and  parts  of 

Optic  Neural  Optic 

depression  plate  depression 


FIG.  494. — Diagram  showing  location  of  optic  areas  before  the  closure  of  the  neural  groove. 

Modified  from  Lange. 

their  modified  anterior  extensions,  the  cornea,  ciliary  body  and  iris,  are  of 
mesodermic  origin.  In  the  sensory  divisions  of  the  other  spinal  and  cranial 
nerves,  with  the  exception  of  the  olfactory,  the  cell  bodies  of  the  neurones  which 
serve  to  connect  the  receptive  mechanisms  with  the  brain  and  cord  are  located 
in  parts  (the  sensory  ganglia  of  the  cranial  and  spinal  nerves)  which  have  be- 
come separated  from  the  crests  of  the  neural  folds  as  the  latter  fuse  to  form  the 
neural  canal.  In  the  eye  the  cell  bodies  of  these  neurones  are  located  in  the 
retina,  but  the  area  of  ectoderm  from  which  the  retina  develops  first  occupies'a 
position  along  the  neural  crest  analogous  to  that  occupied  by  the  anlagen  of  the 
spinal  and  cranial  ganglia.  In  the  case  of  the  retina  this  area,  instead  of  be- 
coming split  off  in  the  closure  of  the  neural  canal,  becomes  folded  into  the 
canal  and  later  pushed  out  toward  the  surface  in  the  optic  evagination  (Figs.  494, 
495,  496)- 

563 


564 


TEXT-BOOK  OF  EMBRYOLOGY. 


The  first  indication  of  eye  formation  is  found  in  the  chick  at  the  beginning 
of  the  second  day  of  incubation ;  in  the  human  embryo,  at  what  has  been  estimated 
as  about  the  second  or  third  week.  At  this  stage  the  neural  canal  is  not  yet 
completely  closed  in  and  its  anterior  end  shows  three  primary  brain  vesicles 


Optic  vesicle  area 


Neural  canal 

FIG.  495. — Diagram  showing  location  of  areas  shown  in  Fig.  494  after  the  formation  of  the 
neural  canal.     Modified  from  Lange. 

(p.  473,  Fig.  497).  The  anlagen  of  the  eyes  first  appear  as  bilaterally  sym- 
metrical evaginations  from  the  lateral  walls  of  the  fore-brain  vesicle  (Figs.  497  and 
498),  and  are  at  first  large  in  proportion  to  the  brain  vesicle  itself.  When 
first  formed,  the  optic  evagination  opens  widely  into  the  fore-brain  vesicle  (Fig. 
498,  right  side),  but  as  the  distal  part  of  the  evagination  expands  more  rapidly 


Retina 


H-b, 


Optic  stalk 


FIG.  496.  FIG.  497. 

FIG.  496.  —  Diagram  showing  location  of  the  (dark)  optic  area  (see  Fig.  495)  after  the  beginning  of 
the  formation  of  the  optic  cup  and  optic  stalk.     Lange. 

FIG.  497.  —  Dorsal  view  of  head  of  chick  of  58  hours'  incubation.     Mihalkovics. 

Lam.  term,  lamina  terminalis;  Fb.,  fore-brain;  Opt.  v.,  optic  vesicle;  M.  b.,  mid-brain; 

H.b.,  hind  or  rhombic  brain;  H.,  heart. 

than  the  proximal  part,  there  soon  results  a  spheroidal  optic  vesicle  attached  to 
the  fore-brain  by  the  narrow  optic  stalk  (Fig.  498,  left  side)  .  Through  the  latter 
the  cavity  of  the  optic  vesicle  and  the  cavity  of  the  fore-brain  are  in  communi- 
cation. With  the  development  of  the  hemispheres,  that  part  of  the  brain  to 
which  the  optic  stalks  are  attached  becomes  the  inter-brain  (diencephalon). 


THE   ORGANS   OF  SPECIAL  SENSE. 


565 


The  Lens. — As  each  optic  vesicle  grows  out  toward  the  surface,  its  outer 
wall  soon  comes  to  lie  just  beneath  the  surface  ectoderm.  The  cells  of  that 
portion  of  the  ectoderm  which  overlies  the  optic  vesicle  next  proliferate  and 
cause  a  thickening  of  the  ectoderm  (Fig.  498,  left  side).  This  thickening  of  the 


Fore-brain  vesicle 


Lens  area  - 


Optic  vesicle 


Surface  ectoderm 


Optic  vesicle 


FIG.  498. — Section  through  head  of  chick  of  two  days'  incubation.    Duval. 

The  formation  of  the  optic  vesicle  and  stalk  appears  to  be  somewhat  more  advanced 

on  the  left  than  on  the  right. 

ectoderm  over  the  optic  vesicle  is  apparent  in  the  chick  embryo  of  36  hours  in- 
cubation; in  the  human  embryo  it  occurs  about  the  third  or  fourth  week  and 
represents  the  first  step  in  the  development  of  the  crystalline  lens.  The  thick- 
ened portion  of  ectoderm  is  known  as  the  lens  area  (Fig.  498).  The  latter  next 

Fore-brain 


Lens  in vagination -gil§      HT: - §f  ^k' '.$   M'^'I*  Lens  invagination 

Optic  vesicle 

Optic  vesicle 

FIG.  499. — Section  through  head  of  chick  of  three  days'  incubation.     Duval. 

becomes  depressed  against  the  outer  surface  of  the  optic  vesicle  forming  a 
distinct  lens  invagination  (Fig.  499).  This  becomes  cup-shaped  and  then  its 
edges  come  together  and  fuse,  thus  forming  the  lens  vesicle  (Fig.  500) .  At  first  the 
lens  vesicle  is  connected  with  the  surface  ectoderm,  but  about  the  eighth  week 


566  TEXT-BOOK  OF  EMBRYOLOGY. 

a  thin  layer  of  mesoderm  grows  in  between  the  lens  vesicle  and  the  surface 
ectoderm,  completely  separating  them  (Fig.  501).  The  ingrowth  of  the  lens 
vesicle  against  the  outgrowing  optic  vesicle  has  the  effect  as  though  a  small  hard 
ball  (the  lens  vesicle)  had  been  pressed  into  a  larger  soft  ball  (the  optic  vesicle) 


Fore-brain 


FIG.  500.  —  Showing  somewhat  later  stage  in  development  of  optic  cup  and  lens 
than  is  shown  in  Fig.  499.     Duval. 

(Fig.  502).  The  lens  vesicle  pushes  the  outer  wall  of  the  optic  vesicle  in  against 
the  inner  wall,  the  optic  vesicle  thus  becoming  transformed  into  the  two-layered 
optic  cup  (Figs.  500,  501).  Bonnet  calls  attention  to  the  fact  that  the  two  proc- 
esses, lens  formation  and  the  invagination  of  the  optic  vesicle  to  form  the  optic 


Conjunctival  epithelium    --- 


Vitreous  — 


Retina  (inner  layer 
of  optic  cup) 

Pigmented  layer  of  retina 
(outer  layer  of  optic  cup) 

FIG.  501.  —  Diagram  of  developing  lens  and  optic  cup.     Duval. 

The  cells  of  the  inner  wall  of  the  lens  vesicle  have  begun  lo  elongate  to  form  lens  fibers.  The  epi- 
thelium over  the  lens  is  the  anlage  of  the  corneal  epithelium.  The  mesodermal  tissue  between 
the  latter  and  the  anterior  wall  of  the  lens  vesicle  is  the  anlage  of  the  substantia  propria 
corneae. 

cup,  are  more  or  less  independent  and  that  it  is  not  correct  to  describe  the  lens  as 
actually  pushing  in  the  outer  wall  of  the  vesicle.  As  evidence  of  this  is  noted 
the  fact  that  typical  optic  cup  formation  may  occur  in  cases  where  no  lens  is 
developed.  The  optic  cup  when  first  formed  is  not  a  complete  cup,  for  the 


THE  ORGANS   OF  SPECIAL  SENSE.  567 

imagination  of  the  optic  vesicle  is  carried  over  along  the  posterior  surface  of  the 
optic  stalk  forming  the  chorioidal  fissure  (Fig.  502,  see  also  p.  575). 

The  lens  area  is  thicker  at  its  center  than  at  its  periphery  and  when  the 
center  of  the  lens  area  becomes  the  bottom  of  the  lens  depression  and  later 
the  posterior  wall  of  the  lens  vesicle  this  greater  thickness  is  maintained.  In 
fact,  the  posterior  wall  of  the  vesicle  becomes  still  thicker  so  that  it  projects  into 
the  cavity  of  the  lens  vesicle  as  an  eminence  (Fig.  503,  g.) .  In  the  chick  the  lens 
vesicle  is  hollow.  In  man  and  in  Mammals  generally  it  is  more  or  less  filled 
with  cells.  These,  however,  degenerate  and  take  no  part  in  the  formation  of  the 

Pigmented  layer  of  retina  Nervous  layer  of  retina 

(outer  layer  of  optic  cup)          (inner  layer  of  optic  cup) 


Cavity  of 
optic  vesicle     ^  ^  ___*_ 

Rim  of  optic  cup. 


Optic  furrow       

Lens 


Hyaloid  artery  I      Optic  furrow 

Hyaloid  artery  entering 
cavity  of  vitreous 

FIG.  502. — Model  showing  lens  and  formation  of  optic  cup.  A  piece  has  been  removed  from  the 
upper  part  of  cup  to  show  the  cavity  of  the  optic  vesicle  and  the  position  of  the  inner  layer 
of  the  cup  (nervous  layer  of  retina) .  Bonnet. 

permanent  lens.  Comparing  the  posterior  with  the  anterior  wall  of  the  lens  at  this 
stage,  the  latter  is  seen  to  be  composed  of  a  single  layer  of  cuboidal  cells,  the  an- 
lage  of  the  anterior  epithelium  of  the  lens  (Figs.  501 ,  503 ,  g,  h,  i) .  This  layer  passes 
over  rather  abruptly  into  the  posterior  wall  which  consists  of  a  single  layer  of 
greatly  elongated  lens  cells,  the  anlagen  of  the  lens  fibers.  The  lens  fibers  con- 
tinue to  elongate  until  by  the  end  of  the  second  month  they  touch  the  anterior 
epithelium,  thus  completely  obliterating  the  cavity  of  the  lens  vesicle  (Fig.  505). 
A  small  cleft  containing  a  few  drops  of  fluid,  the  liquor  Morgagni,  may  remain 
between  the  anterior  epithelium  and  the  lens  fibers. 

When  the  lens  fibers  are  first  formed,  the  longest  fibers  are  in  the  center  and 
the  fibers  gradually  get  shorter  toward  the  periphery  of  the  lens  where  they  pass 
over  into  the  anterior  epithelium  (Fig.  503),  As  the  lens  develops,  the  periph- 


568 


TEXT-BOOK  OF  EMBRYOLOGY. 


eral  fibers  elongate  more  rapidly  than  the  central,  with  the  result  that  in  the  fully 
developed  lens  the  central  fibers  are  the  shortest,  forming  a  sort  of  core  around 
which  the  now  longer  peripheral  fibers  extend  in  much  the  same  manner  as  the 
layers  of  an  onion  (Fig.  505) .  The  ends  of  the  fibers  meet  on  the  anterior  and 
posterior  surfaces  of  the  lens,  along  more  or  less  definite  lines  which  can  be  seen 


FIG.  503. — Successive  stages  in  the  development  of  the  lens  in  the  rabbit  embryo.     Rdbl. 

a,  b,  c,  d,  and  e,  are  from  embryos  of  from  n|  to  12  days;  f,  at  end  of  i2th  day;  g,  during  the  i3th 

day;   h,  between  the  i3th  and  i4th  days;  i,  from  an  embryo  of  n  mm. 

on  surface  examination  and  which  are  known  as  sutural  lines.  The  lens  fibers 
are  at  first  all  nucleated  and  as  the  nuclei  are  situated  at  approximately  the  same 
level  in  all  the  fibers,  there  results  a  so-called  nuclear  zone  (Fig.  503,  i).  Later 
the  nuclei  disappear.  The  sutural  lines  become  evident  about  the  fifth  month 
and  mark  the  completion  of  the  lens  formation,  although  lens  fibers  continue 
to  be  formed  throughout  foetal  and  in  postnatal  life,  probably  by  proliferation 


THE  ORGANS   OF  SPECIAL  SENSE  569 

and  differentiation  of  the  cells  of  the  anterior  epithelium,  in  the  region  where  the 
latter  pass  over  into  the  lens  fibers.  (The  successive  stages  in  the  development 
of  the  lens  are  shown  in  Fig.  503.) 

The  lens  capsule  becomes  differentiated  during  the  third  month.  It  is  con- 
sidered by  some  as  derived  from  the  lens  epithelium  and  of  the  nature  of  a 
cuticular  membrane,  by  others  as  a  product  of  the  surrounding  connective 
tissue. 

By  the  extension  of  mesodermic  tissue  in  between  the  lens  and  the  surface 
ectoderm,  the  lens  becomes  by  the  end  of  the  sixth  week  completely  surrounded 
by  a  layer  of  vascular  connective  tissue.  This  is  known  as  the  tunica  vasculosa 
lentis,  and  receives  its  blood  supply  mainly  from  the  hyaloid  artery  (Fig.  505) 
which  is  a  foetal  continuation  of  the  arteria  centralis  retina  (p.  575).  Branches 
from  the  hyaloid  artery  break  up  into  a  capillary  network  which  covers  both 
anterior  and  posterior  surfaces  of  the  lens.  That  part  of  the  tunica  vasculosa 
which  covers  the  anterior  surface  of  the  lens  is  known  as  the  membrana  pupillaris. 
After  the  earlier  and  more  rapid  formation  of  lens  fibers  ceases,  the  hyaloid 
artery  begins  (about  the  seventh  month)  to  undergo  regressive  changes,  and  at 
birth  is  normally  absent.  Rarely  more  or  less  of  the  tunica  vasculosa  fails  to 
degenerate,  and  if  the  part  wrhich  persists  is  the  membrana  pupillaris  there 
results  a  malformation  known  as  congenital  atresia  of  the  pupil. 

The  Optic  Cup. —  The  w^ay  in  which  the  optic  vesicle  becomes  transformed 
into  the  optic  cup  has  been  partially  described  in  considering  the  development  of 
the  lens  (p.  566) .  The  growing  lens  vesicle  appears  to  push  in  the  outer  wall  of 
the  optic  vesicle  while  at  the  same  time  the  edges  of  the  latter  are  extending 
around  the  lens  vesicle,  until  wrhat  was  originally  the  outer  wall  of  the  optic 
vesicle  lies  in  apposition  with  the  original  inner  wall,  the  cavity  of  the  primary 
optic  vesicle  thus  becoming  completely  obliterated  (Fig.  504).  In  this  way  the 
optic  vesicle  is  transformed  into  a  two-layered  thick-wralled  cup,  the  cleft  be- 
tween the  two  layers  corresponding  to  the  cavity  of  the  primary  vesicle.  This 
cup  is  at  first  entirely  filled  with  the  developing  lens  (Fig.  504) .  As  the  cup  in- 
creases in  size  faster  than  the  lens,  the  contiguous  walls  of  the  cup  and  lens 
become  separated,  the  cavity  thus  formed  being  the  cavity  of  the  vitreous 
humor  (Fig.  505).  There  seems  to  be  no  question  but  that  in  Mammals  a 
small  amount  of  mesoderm  at  first  separates  the  optic  evagination  from  the  lens 
area  of  the  surface  ectoderm.  This  apparently  disappears,  however,  so  that 
the  two  are  in  direct  contact.  It  is  still  an  open  question  whether  a  thin  layer 
of  mesoderm  grows  in  between  the  edges  of  the  cup  and  the  lens  at  or  just  before 
the  beginning  of  the  formation  of  the  vitreous.  The  lens  now  no  longer  fills  the 
optic  cup  but  lies  in  the  mouth  of  the  cup,  while  at  the  same  time  the  margin 
of  the  cup  is  extending  somewhat  over  its  outer  surface,  where  with  the  meso- 
derm it  ultimately  gives  rise  to  the  ciliary  body  and  iris,  and  forms  the 


570 


TEXT-BOOK  OF  EMBRYOLOGY. 


boundary  of  the  pupil.     The  remainder  of  the  two-walled  optic  cup  becomes 
the  retina. 

The  Retina. — Of  the  two  layers  which  form  the  wall  of  the  optic  cup  (p.  569) , 
the  outer  (away  from  the  cavity)  forms  thepigmented  layer,  while  the  inner  forms 
the  remainder  of  the  retina  (Figs.  501,  505).  Soon  after  the  formation  of  the 
optic  cup,  it  is  possible  to  distinguish  a  boundary  zone — the  future  or  a  serrata— 
between  the  larger  posterior  part  of  the  retina  or  nervous  retina  and  the  smaller 
anterior  non-nervous  part  which  becomes  the  retinal  portion  of  the  ciliary  body 


Vascular  mesoderm 


[Remains  of  optic 
vesicle  cavity 


Ectoderm 


Lens  anlage 
Lens  invagination 


Pigmented  layer  of  retina 
(outer  layer  of  optic  cup) 


Vascular  mesoderm 
Wall  of  brain  vesicle 


FIG.  504. — Section  through  optic  cup  and  lens  invagination  of  chick  of  fifty-four 

hours'  incubation.     Lange. 

Between  the  lens  anlage  and  the  pigmented  layer  of  the  retina  is  the  broad  inner  layer  of  the  optic 
cup,  the  anlage  of  the  remainder  of  the  retina. 

and  iris.  While  the  optic  cup  is  forming,  its  two  layers  are  both  rapidly  in- 
creasing in  thickness  by  mitotic  division  of  their  cells.  Especially  is  this  true  of 
the  inner  layer  over  that  region  which  is  to  become  the  nervous  retina,  and  it  is 
the  rather  abrupt  transition  between  the  thicker  nervous  retina  and  the  com- 
paratively thin  non-nervous  anterior  extension  of  the  retina  that  forms  the  ora 
serrata. 

The  invagination  which  gives  rise  to  the  two-layered  optic  cup  thus  differen- 
tiates what  may  be  called  the  two  primary  layers  of  the  retina,  the  pigmented  layer, 
and  a  broad  layer  from  which  are  to  develop  all  the  other  layers  of  the  retina. 


THE  ORGANS   OF  SPECIAL  SENSE. 


571 


(Figs.  501 , 505) .  Further  development  consists  in  a  gradual  differentiation,  within 
the  broad  layer,  of  the  various  retinal  elements  and  consequent  demarcation  of  the 
layers  which  constitute  the  adult  retina.  The  next  layer  to  differentiate  is  the 
innermost  layer  of  the  retina,  or  layer  of  nerve  fibers.  This  appears  during  the 
sixth  or  seventh  week  as  a  thin,  clear,  faintly  striated  zone  containing  a  few 
scattered  nuclei.  What  remains  of  the  original  inner  layer  of  the  cup  has  now 
become  a  comparatively  thick  layer  with  numerous  chromatic  and  actively 
dividing  nuclei.  It  may  be  conveniently  designated  the  primitive  nuclear  layer. 


Surface  epithelium 

of  eyelid 

Eyelid  (upper) 

Corneal  epithelium 

Conjunct!  val 

epithelium 

Substantia 

propria  corneae 

Lens 

Anterior  epithe- 
lium of  lens 

Conjunctival  sac 


Chorioid 
Pigmented  layer 
of  retina 
Split  between 
retinal  layers 
Retina,  except 
pigmented  layer 
Vitreous 

Tunica  vasculosa 

lentis 

Nerve  fiber  layer 

of  retina 


Hyaloid  artery 

Central  artery 
of  retina 

Optic  nerve 


FIG.  505. — Horizontal  section  through  eye  of  human  embryo  of  13-14  weeks.     Modified  from  Lange. 

The  similarity  in  development  between  the  retina  and  wall  of  the  neural  tube 
is  to  be  noted.  Thus  the  layer  of  nerve  fibers  appears  to  correspond  quite 
closely  to  the  marginal  layer  of  the  central  nervous  system,  while  the  primitive 
nuclear  layer  is  probably  homologous  with  the  mantle  layer  (pp.  479,  485). 
There  is  a  similar  correspondence  between  the  retina  and  the  central  nervous 
system  in  regard  to  their  early  cellular  development,  the  retinal  cells  early 
showing  a  differentiation  into  neuroblasts  and  spongiobiasts  (pp.  479,  485). 

About  the  end  of  the  eighth  week  the  inner  part  of  the  primitive  nuclear 
layer  differentiates  into  the  layer  of  ganglion  cells  (Fig.  506,  It).  These 
are  large  cells  and  with  their  processes  constitute  the  third  or  proximal  optic 
neurone.  They  can  be  first  distinguished  in  the  fundus  of  the  cup  and  gradu- 
ally extend  to  the  ora  serrata.  They  are  the  first  of  the  cellular  elements  of  the 
adult  retina  which  can  be  definitely  recognized  as  such.  From  each  cell,  two 
kinds  of  processes  develop,  dendrites,  which  ramify  in  this  and  in  the  more 
external  layers  of  the  retina,  and  an  axone  which  grows  toward  the  cavity  of 
the  eye  and  becomes  a  fiber  of  the  layer  of  nerve  fibers,  whence  it  continues  into 


572 


TEXT-BOOK  OF  EMBRYOLOGY. 


the  optic  stalk  as  one  of  the  fibers  of  the  optic  nerve.  The  layer  of  ganglion  cells 
is  thickest  in  an  area  situated  somewhat  lateral  to  the  attachment  of  the  optic 
stalk  and  known  as  the  area  centralis.  It  is  distinguishable  about  the  end  of  the 
fourth  month.  In  the  center  of  the  area  centralis  the  retinal  layers  become 
thin  to  form  ihefovea  centralis  which  develops  toward  the  end  of  fcetal  life. 
The  macula  lutea  with  its  yellow  pigment  does  not  develop  until  after  birth. 
The  retina  at  this  stage  thus  consists  of  four  layers  which  from  within  out- 
ward are  (i)  the  layer  of  nerve  fibers,  (2)  the  layer  of  ganglion  cells,  (3)  the 
nuclear  layer,  (4)  the  pigmented  layer  (see  Fig.  507) . 


FIG.  506. — Diagram  of  the  development  of  the  retinal  cells.     Kallius,  after  Cajal. 
a,  Cone  cells  in  unipolar  stage;  b,  cone  cells  in  bipolar  stage;  c,  rod  cells  in  unipolar  stage;  d,  rod  cells 
in  bipolar  stage;  e,  bipolar  cells;  /and  i,  amacrine  cells;  g,  horizontal  cell;  h,  ganglion  cells; 
k,  Muller's  cells  or  fibers;  I,  external  limiting  membrane. 

The  further  development  of  the  retina  consists  largely  of  a  differentiation  of 
the  cells  of  the  nuclear  layer.  This  is  extremely  complex  and  our  knowledge 
of  it  meager.  From  the  cells  of  this  layer  develop  (i)  the  rod  and  cone  cells,  (2) 
the  bipolar  cells,  (3)  the  tangential  or  horizontal  cells,  (4)  the  amacrine  cells,  (5) 
Muller's  cells  or  fibers.  The  differentiation  of  these  cells  and  their  processes 
also  results  in  the  demarcation  of  the  following  layers  of  the  adult  retina;  (i)  the 
layer  of  rods  and  cones,  (2)  the  outer  limiting  membrane,  (3)  the  outer  nuclear 
layer,  (4)  the  outer  molecular  layer,  (5)  the  inner  nuclear  layer,  (6)  the  inner 
molecular  layer,  (7)  the  inner  limiting  membrane  (see  Fig.  508). 

Muller's  cells  or  the  sustentacular  cells  (Fig.  506,  k)  develop  from  spongio- 
blasts  which  lie  toward  the  inner  limit  of  the  nuclear  layer.  This  accounts 
for  the  location  of  the  nucleated  portions  of  Muller's  cells.  Processes  of  these 
cells  grow  toward  both  surfaces  of  the  retina  until  they  reach  the  positions  of  the 
future  outer  and  inner  limiting  membranes  where  they  are  believed  to  spread  out 


THE   ORGANS  OF  SPECIAL  SENSE.  573 

horizontally  and  unite  to  form  these  membranes.  Other  spongioblasts  develop 
into  other  types  of  glia  cells,  mainly  spider  cells,  which  are  most  numerous  in 
the  layer  of  ganglion  cells  and  in  the  layer  of  nerve  fibers. 

The  rod  and  cone  cells  are  first  recognizable  as  unipolar  cells  (Fig.  506,0,  c). 
The  single  process  of  each  extends  outward  as  far  as  the  outer  limiting  mem- 
brane. About  as  soon  as  these  cells  are  recognizable,  a  differentiation  between 
the  rod  cells  and  the  cone  cells  can  be  made  by  their  reactions  to  the  Golgi 
silver  stain,  the  cone  cells  impregnating  much  more  completely  than  the  rod 
cells.  Processes  next  grow  out  from  the  inner  ends  of  the  cells  so  that  they 
become  bipolar  (Fig.  506,  b,  d).  Both  rod  and  cone  cells  are  at  first  distributed 
throughout  the  entire  nuclear  layer,  but  later  they  become  arranged  in  a  dis- 
tinct layer  just  beneath  the  outer  limiting  membrane.  Each  cell  next  gives 
rise  to  or  acquires  at  its  outer  end  an  expansion  which  extends  through 

Layer  of  nerve  fibers 
Layer  of  nerve  cells 
Inner  molecular  layer 
Inner  nuclear  layer 


w¥;ww?» 
inpfiK^ 

KFJzras^ 

nil 


Outer  undifferentiated  layer 


FIG.  507. — Vertical  section  through  retina  of  a  four  months'  human  embryo.    Modified  from  Lange* 

the  outer  limiting  membrane  into  the  pigmented  layer.  As  the  pigmented 
cells  give  off  pigmented  processes  which  extend  inward  among  the  outer 
ends  of  the  rods  and  cones,  the  layer  of  retina  just  beneath  the  pig- 
mented layer  consists  of  the  outer  ends  of  the  rod  cells,  the  tips  of  the  cone 
cells,  and  the  extensions  of  the  pigmented  cells.  The  nucleated  portions  of 
the  rod  and  cone  cells  form  the  outer  nuclear  layer.  Though  the  layer  of  rods 
and  cones  and  the  outer  nuclear  layer  present  the  appearance  in  haematoxylin- 
eosin  stained  specimens  of  two  distinct  layers,  it  is  evident  from  their  develop- 
ment and  structure  that  they  should  be  regarded  as  a  single  neuro- epithelial 
layer.  The  apparent  separation  into  two  layers  is  due  to  the  interposition  of  the 
outer  limiting  membrane,  through  tiny  holes  in  which  the  rod  and  cone  cells 
extend.  The  inwardly  directed  processes  of  the  rod  and  cone  cells  are  their 
axones.  These  cells  constitute  the  first  or  distal  optic  neurone. 

The  bipolar  cells  (Fig.  506,  e),  which  with  their  processes  constitute  the 
middle  or  second  optic  neurone,  also  develop  from  cells  of  the  nuclear  layer 


574 


TEXT-BOOK  OF  EMBRYOLOGY. 


and  are  probably  bipolar  at  the  time  that  the  rod  and  cone  cells  are  in  the 
unipolar  condition.  Reference  to  the  two  bipolar  cells  shown  in  Fig.  506,  e,  e, 
shows  that  at  this  stage  in  their  development  their  outwardly  directed  processes 
extend  to  the  outer  limiting  membrane.  These  processes  must  either  actually 
shorten  or  else  fail  to  grow  in  length  proportionately  as  the  retina  increases  in 
thickness,  for  in  the  mature  retina  they  end  in  relation  with  the  centrally 
(inwardly)  directed  processes  (axones)  of  the  rod  and  cone  cells.  According  as 
they  are  in  relation  with  rod  cells  or  cone  cells,  they  are  known  as  rod  bipolars 
or  cone  bipolars.  The  retinal  layer  in  which  the  axones  of  the  rod  and  cone 

Inner  limiting  membrane 


Layer  of  nerve  fibers 
Layer  of  nerve  cells 

Inner  molecular  layer 

( horizontal  cells 

Inner  nuclear  layer  ^  bipolar  cells 
(amacrine  cells 

Outer  molecular  layer 
Outer  nuclear  layer 

Outer  limiting  membrane 
Layer  of  rods  and  cones 


Layer  of  pigmented  epithelium 

FIG.  508. — Vertical  section  through  retina  of  a  five  and  one-half  months'  human  embryo. 

Modified  from  Lange. 

cells  and  the  dendrites  of  the  rod  and  cone  bipolars  intermingle  is  the  outer 
molecular  layer  of  the  adult  retina.  It  is  first  distinctly  recognizable  as  a  mo- 
lecular layer  about  the  end  of  the  fifth  month  (Fig.  508). 

The  development  of  the  outer  molecular  layer  separates  the  originally  single 
nuclear  layer  into  two  layers,  an  outer  composed  of  the  nuclei  of  the  rod  and  cone 
cells  and  an  inner  composed  of  the  nucleated  bodies  of  the  rod  and  cone 
bipolars,  of  the  horizontal  cells  (Fig.  506,  g)  and  of  the  amacrine  cells  (Fig.  506, 
/  and  i),  all  of  which  can  be  recognized  in  Golgi  specimens  by  the  end  of  the 
seventh  month.  The  rod  and  cone  bipolars  and  probably  most  of  the  other 
cells  of  the  inner  nuclear  layer  send  their  axones  centrally  to  lie  in  contact  with 
the  dendrites  and  bodies  of  the  ganglion  cells. 


THE  ORGANS  OF  SPECIAL  SENSE.  575 

With  the  development  of  the  cells  of  the  inner  nuclear  layer  and  their  proc- 
esses, there  differentiates  the  inner  molecular  layer  which  separates  the  inner 
nuclear  layer  and  the  layer  of  ^ganglion  cells.  It  consists  mainly  of  ramifica- 
tions of  the  dendrites  and  axones  of  cells  the  bodies  of  which  lie  in  the  inner 
nuclear  layer  and  in  the  layer  of  ganglion  cells.  (Fig.  508.) 

The  Chorioid  and  Sclera. — These  develop  wholly  from  the  mesoderm. 
The  way  in  which  the  mesoderm  grows  in  between  the  lens  and  the  surface  and 
surrounds  the  optic  cup  has  been  described  (p.  566).  That  part  of  the  meso- 
derm lying  immediately  external  to  the  retina  develops  very  early  a  close- 
meshed  capillary  network.  This  appears  before  there  is  any  definitely  limited 
sclera  and  may  be  considered  the  anlage  of  the  chorioid.  Somewhat  later  the 
mesoderm  which  lies  just  to  the  outside  of  the  chorioid  takes  definite  shape  as  the 
external  fibrous  tunic  of  the  eye  or  sclera. 

The  Vitreous. — The  manner  in  which  the  vitreous  humor  is  formed  has 
been  the  subject  of  much  controversy  and  remains  still  undetermined.  As 
already  noted  in  describing  the  development  of  the  lens  (p.  585),  the  latter  is  at 
first  in  direct  contact  with  the  inner  layer  of  the  retina  (Fig.  504) .  The  lens  and 
the  retina  separate  as  the  vitreous  forms  between  them.  During  the  develop- 
ment of  the  lens  the  arteria  centralis  retinas  does  not  stop,  as  in  the  adult, 
with  its  retinal  branches,  but  continues  across  the  optic  cup  as  the  hyaloid 
artery  to  end  in  the  vessels  of  the  tunica  vasculosa  lentis.  Some  investigators 
consider  the  vitreous  a  transudate  from  these  blood  vessels.  As  the  chorioidal 
fissure  closes,  some  mesodermic  tissue  is  enclosed  with  the  artery,  and  some 
investigators  consider  the  vitreous  a  derivative  of  this  mesoderm.  In  Birds 
the  formation  of  the  vitreous  humor  begins  before  either  mesoderm  or  blood 
vessels  have  penetrated  the  optic  cup,  and  Rabl  suggests  that  the  vitreous  may 
be  a  secretion  of  the  retinal  cells.  Bonnet  describes  a  double  origin  of  the 
vitreous,  differentiating  between  a  retinal  vitreous  and  a  mesoderm  vitreous. 
According  to  Bonnet,  the  primary  vitreous  body  begins  its  formation  before  the 
closure  of  the  chorioidal  fissure.  This  primary  vitreous  appears  at  the  time 
of  formation  of  the  optic  cup,  is  a  fibrillated  secretion  of  the  retinal  cells,  and 
fills  in  the  vitreous  space  with  a  feltwork  of  fine  fibrils.  With  the  formation  of 
the  optic  cup  and  the  closure  of  the  chorioidal  fissure  this  type  of  vitreous  forma- 
tion ceases  and  a  secondary  vitreous  body  formation  takes  place  from  the  cells 
of  the  pars  ciliaris  retinae.  This  is  also  fibrillated  and  there  develops  at  this 
time  the  so-called  hyaloid  membrane  which  closely  invests  the  vitreous.  Among 
the  fibers  of  the  vitreous  body  appears  the  vitreous  humor.  Up  to  this  point  the 
vitreous  is  entirely  non-cellular.  There  next  grow  into  it  mesodermal  cells 
which  have  reached  the  vitreous  through  the  chorioidal  fissure  along  with  the 
hyaloid  artery.  To  what  extent  these  cells  are  used  up  in  the  formation  of  the 
blood  vessels  of  the  vitreous  and  to  what  extent  they  remain  as  connective  tissue 


576  TEXT-BOOK  OF  EMBRYOLOGY. 

cells  of  the  mature  vitreous  after  the  blood  vessels  have  degenerated  is  not 
known. 

As  already  noted,  the  vitreous  is  at  first  crossed  by  the  hyaloid  artery  which 
supplies  the  developing  lens  (p.  569).  As  lens  formation  becomes  less  active 
the  artery  becomes  less  important  and  by  the  end  of  the  third  month  begins  to 
atrophy.  At  birth  nothing  remains  of  it,  but  in  its  former  course  the  vitreous 
is  somewhat  more  fluid  than  elsewhere  and  this  is  known  as  the  hyaloid  canal 
(canal  of  Cloquet). 

The  Optic  Nerve. — Referring  to  the  description  of  the  optic  evagination  it 
will  be  recalled  that  the  optic  vesicle  maintains  its  connection  with  the  brain  by 
means  of  the  optic  stalk  (p.  564).  The  latter  is  hollow  and  connects  the  cavity 
of  the  optic  vesicle  with  the  cavity  of  the  brain.  When  the  invagination  of  the 
optic  vesicle  to  form  the  optic  cup  occurs  (p.  566,  Fig.  502),  the  invagination  is 
carried  along  the  posterior  surface  of  the  optic  stalk  toward  the  brain,  and  just 
as  the  invagination  of  the  optic  vesicle  results  in  the  obliteration  of  the  cavity 
of  the  vesicle,  so  the  invagination  of  the  optic  stalk  results  in  an  oblitera- 
tion of  its  lumen.  In  Mammals  the  invagination  of  the  optic  stalk  extends  only 
part  way  to  the  brain,  to  the  point  where  the  artery  enters.  The  chorioidal 
fissure  closes  about  the  seventh  week. 

The  optic  stalk  consists  of  supportive  elements  only,  and  serves  as  a  track 
along  which  nerve  fibers  extend  to  connect  the  retina  and  brain.  Nerve  fibers 
appear  in  the  optic  stalk  about  the  fifth  week.  They  appear  first  around  the 
periphery  and  apparently  crowd  the  neuroglia  nuclei  toward  the  center,  so  that 
the  stalk  at  this  stage  may  be  said  to  consist  of  a  mantle  layer  and  a  marginal 
layer,  apparently  analogous  to  these  layers  in  the  retina  and  brain.  The  nerve 
fibers  gradually  invade  the  entire  stalk  so  that  by  the  end  of  the  third  month  the 
stalk  has  become  transformed  into  the  optic  nerve  among  the  fibers  of  which  the 
original  supportive  elements  of  the  stalk  are  still  represented  by  neuroglia  cells. 

Much  difference  of  opinion  has  existed  in  regard  to  the  origin  of  the  optic 
nerve  fibers,  whether  they  are  processes  of  retinal  cells  which  end  in  the  brain 
or  processes  of  brain  cells  which  end  in  the  retina.  It  is  now  quite  generally 
accepted  that  most  of  the  fibers  of  the  optic  nerve  are  the  axones  of  neurones  the 
cell  bodies  of  which  are  situated  in  the  ganglion  cell  layer  of  the  retina.  These 
axones  pass  centrally  into  the  layer  of  nerve  fibers,  which  they  form,  and  con- 
verge toward  the  optic  nerve.  Through  the  latter  they  pass  to  their  terminations 
in  the  external  geniculate  bodies,  optic  thalami  and  anterior  corpora  quadri- 
gemina.  According  to  Cajal  and  others,  some  centrifugal  fibers  are  present  in 
the  optic  nerve.  These  are  processes  of  cells  situated  in  the  above-mentioned 
nuclei,  and  terminate  in  the  retina.  They  are  fewer  in  number  and  of  later 
development  than  the  centripetal  fibers. 

As  the  mesodermic  anlagen  of  the  chorioid  and  sclera  are  present  before 


THE  ORGANS   OF  SPECIAL  SENSE.  577 

the  nerve  fibers  begin  to  grow  into  the  optic  stalk,  the  fibers  must  pass  through 
these  two  coats  in  their  exit  from  the  eye.  There  results  the  fenestrated  cross- 
ing of  the  optic  nerve  by  these  two  coats,  known  as  the  lamina  cribrosa. 

The  optic  nerve  fibers  are  medullated  but  have  no  neurilemmae.  They  are 
supported  by  neuroglia.  The  connective  tissue  sheaths  which  enclose  the  optic 
nerve  are  direct  extensions  of  the  meninges.  These  structural  peculiarities 
accord  with  the  peculiarities  already  described  in  the  development  of  the 
nerve.  Attention  has  been  called  to  the  fact  (p.  563)  that  just  as  the  retina 
should  be  considered  a  modified  and  displaced  portion  of  the  central  nervous 
system — of  brain  cortex — so  the  optic  nerve  should  be  considered  not  as  a 
peripheral  nerve,  but  as  analogous  to  a  central  nervous  system  fiber  tract. 

The  Ciliary  Body,  Iris,  Cornea,  Anterior  Chamber. — Anteriorly  where 
they  come  into  relation  with  the  lens  and  are  so  arranged  as  to  admit  light  to  the 
retina,  all  three  coats  of  the  eye  are  extensively  modified.  Thus  the  retina  is 
continued  anteriorly  as  the  pars  ciliaris  retinae  and  pars  iridica  retinae,  the 
chorioid  as  the  stroma  of  the  ciliary  body  and  iris,  the  sclera  as  the  cornea. 

THE  CILIARY  BODY  AND  IRIS. — Both  primary  retinal  layers  (the  two  layers 
of  the  optic  cup)  are  continued  anteriorly  as  the  non-nervous  retinal  layer 
of  the  ciliary  body  and  iris.  The  outer  pigmented  layer  consists  at  first  of 
several  layers  of  pigmented  cells,  but  later  becomes  reduced  to  a  single  layer 
of  pigmented  cells  which  do  not,  however,  possess  pigmented  processes  extend- 
ing inward  as  do  the  analogous  cells  of  the  nervous  retina.  The  abrupt  tran- 
sition at  the  ora  serrata  where  the  thick  pars  optica  retinae  passes  over  into  the 
pars  ciliaris  retinae  has  been  mentioned  (p.  570).  The  inner  layer  of  the  primi- 
tive retina  (optic  cup)  extends  over  the  ciliary  body  and  iris  as  a  single  layer  of 
cells.  These  remain  non-pigmented  over  the  ciliary  body,  but  over  the  iris 
acquire  pigment  so  that  the  two  layers  form  the  pigmented  layer  of  the  iris. 

The  mesodermic  tissue  which  forms  the  stroma  of  the  ciliary  body  and  iris 
is  derived  from  the  mesoderm  lying  between  the  lens  and  the  surface  ectoderm. 
This  separates  into  two  layers  enclosing  between  them  the  anterior  chamber  of 
the  eye,  and  it  is  from  the  posterior  of  these  twro  layers  that  mesodermic  tissue 
extends  into  the  ciliary  body  and  iris.  It  is  continuous  with  the  mesoderm  of 
the  tunica  vasculosa  lentis.  During  the  fourth  month  the  ciliary  body  under- 
goes foldings  to  form  the  ciliary  processes.  These  foldings  at  first  involve 
also  the  iris,  but  the  iris  folds  soon  (end  of  fifth  month)  disappear,  while  the 
ciliary  processes  become  more  prominent. 

Of  the  smooth  muscle  tissue  found  in  the  ciliary  body  and  iris,  the  dilator 
and  contractor  pupillae  are,  according  to  Bonnet,  derived  from  the  cells  of  the 
pigmented  layer  of  the  retina,  i.e.,  from  ectoderm.  The  ciliary  muscle,  on  the 
other  hand,  develops  from  mesoderm.  These  muscles  become  well  developed 
during  the  seventh  month. 


.578  TEXT-BOOK  OF  EMBRYOLOGY. 

The  suspensory  ligament  of  the  lens,  or  zonula  Zinnii,  first  appears  about  the 
end  of  the  fourth  month.  By  some  the  fibers  of  the  suspensory  ligament 
are  believed  to  differentiate  from  the  vitreous,  by  others  they  are  considered  as 
derived  from  the  pars  ciliaris  retinae.  Spaces  among  the  fibers  of  the  ligament 
enlarge  and  coalesce  to  form  the  canal  of  Petit. 

THE  CORNEA. — The  way  in  which  the  mesoderm  grows  in  between  the  lens 
vesicle  and  the  surface  ectoderm  has  been  described  (p.  566).  This  mesoderm 
forms  a  thin  almost  homogeneous  layer  containing  very  few  cells.  Later  that 
part  of  the  layer  which  lies  against  the  lens  becomes  more  cellular  and  vascular, 
so  that  it  is  possible  to  distinguish  between  an  outer  homogeneous  non- vascular 
layer  and  an  inner  cellular  vascular  layer.  The  former  is  the  anlage  of  the 
cornea.  Between  the  two  layers  vacuoles  appear  and  coalesce  to  form  the 
anterior  chamber  of  the  eye  or  cavity  of  the  aqueous  humor.  Subsequent 
growth  of  the  iris  subdivides  this  chamber  into  an  anterior  and  a  posterior 
portion.  The  chamber  separates  the  cornea  from  the  pupillary  membrane 
portion  of  the  tunica  vasculosa  lentis.  Bounding  the  chamber  anteriorly  and 
so  forming  the  posterior  layer  of  the  cornea  there  develops  a  single  layer  of 
flat  cells,  the  so-called  " endothelium"  of  Descemet.  Over  the  surface  of  the 
cornea  the  ectoderm  remains  and  gives  rise  to  a  stratified  squamous  epithelium 
four  to  eight  cells  thick,  the  anterior  corneal  epithelium.  Just  beneath  the 
epithelium  a  layer  of  corneal  tissue  retains  its  original  homogeneous  character 
and  forms  the  anterior  elastic  membrane  or  membrane  of  Bowman.  The 
posterior  elastic  membrane  or  membrane  of  Descemet  is  usually  considered  a 
cuticular  derivative  of  the  "  endothelium.''  Throughout  the  rest  of  the  cornea 
— substantia  propria  cornece — cells  develop,  either  by  proliferation  of  the 
few  cells  originally  present  or  from  cells  which  grow  in  from  the  surrounding 
cellular  mesoderm,  and  become  arranged  parallel  to  the  surface  as  the  fixed 
connective  cells  of  the  cornea. 

The  Eyelids. — After  the  lens  vesicle  becomes  separated  from  the  surface 
ectoderm,  the  latter  folds  over  above  and  below  to  form  the  first  rudiments 
of  the  upper  and  lower  eyelids.  Each  fold  consists  of  a  core  of  mesoderm  and 
a  covering  of  ectoderm.  From  the  mesoderm  develop  the  connective  tissue 
elements  of  the  lids  including  the  tarsal  cartilage.  From  the  ectoderm  develop 
the  epithelial  structures  of  the  lids,  the  epidermis,  the  eyelashes  and  the  glands. 
The  edges  of  the  lids  gradually  approach  each  other  and  about  the  beginning 
of  the  third  month  the  epithelium  of  the  upper  lid  becomes  adherent  to  that 
of  the  lower,  thus  completely  shutting  in  the  eyeball.  This  condition  obtains 
until  just  before  birth. 

The  eyelashes  develop  in  the  same  manner  as  other  hairs  (p.  447). 

The  Meibomian  glands,  glands  of  Moll  and  the  lacrymal  glands  develop, 
during  the  period  the  lids  are  adherent,  as  solid  cords  of  ectoderm  which  giow 


THE   ORGANS  OF  SPECIAL  SENSE.  579 

into  the  underlying  mesoderm  where  they  ramify  to  form  the  ducts  and  tubules. 
The  anlagen  of  the  ducts  and  tubules  of  these  glands  are  thus  at  first  solid  cords 
of  cells,  their  lumina  being  formed  later  by  a  breaking  down  of  the  central  cells 
of  the  cords. 

At  the  inner  angle  of  the  conjunctiva  there  develops  beneath  the  eyelid 
folds  a  third  much  smaller  fold.  This  becomes  the  plica  semilunaris  which 
in  man  is  a  rudimentary  structure,  but  in  many  of  the  lower  Vertebrates, 
especially  Birds,  forms  a  distinct  third  eyelid,  the  so-called  nictitating  mem- 
brane. A  few  hair  follicles  and  sebaceous  glands  develop  in  a  portion  of  this 
fold  forming  the  lacrymal  caruncle. 

The  Lacrymal  Duct.  At  a  certain  stage  in  development,  a  groove  bounded 
by  the  maxillary  process  and  the  lateral  nasal  process  extends  from  the  eye  to 
the  nose  (Fig.  136).  This  is  known  as  the  naso-optic  furrow.  The  ectoderm 
(epithelium)  lying  along  the  bottom  of  this  groove  thickens  about  the  sixth 
week  and  forms  a  solid  cord  of  cells.  As  development  proceeds  and  the  parts 
close  in,  this  cord  of  ectoderm  becomes  enclosed  within  the  mesoderm,  excepting 
at  its  ends  where  it  remains  connected  with  the  surface  ectoderm  of  the  eye  and 
nose,  respectively.  By  a  breaking  down  of  the  central  cells  of  this  cord  a  lumen 
is  formed  and  the  cord  becomes  a  tube,  the  lacrymal  duct.  The  primary  con- 
nection of  the  lacrymal  duct  is  with  the  upper  lid,  but  while  the  lumen  is  being 
formed  an  offshoot  grows  out  to  the  under  eyelid  to  form  the  inferior  branch 
of  the  lacrymal  duct. 

THE  NOSE. 

The  anlage  of  the  organ  of  smell  is  apparent  in  human  embryos  of  about 
three  weeks  as  two  thickenings  of  the  ectoderm,  one  on  each  side  of  the  naso- 
frontal  process.  To  these  thickenings  the  term  olfactory  placodes  has  been 
applied  (Kupffer).  A  little  later  (in  embryos  of  about  four  weeks),  the  placodes 
become  depressed  below  the  surface,  the  depressions  themselves  being  the 
nasal  pits  or  fossa  (see  p.  148;  also  Fig.  123).  The  placodes,  which  are 
destined  to  give  rise  to  the  sensory  epithelium,  thus  come  into  closer  relation 
with  the  olfactory  lobes  of  the  brain  (rhinencephalon)  which  represent  out- 
growths of  the  fore-brain  (telencephalon)  (see  p.  501). 

As  described  in  connection  with  the  development  of  the  face,  the  lateral 
nasal  process  arises  on  the  lateral  side,  the  medial  nasal  process  on  the  medial 
side,  of  each  nasal  pit  (p.  148  et  seq.;  also  Fig.  134).  Of  these  processes,  the 
lateral  is  destined  to  give  rise  to  the  lateral  nasal  wall  and  the  wing  of  the  nose, 
the  medial  to  a  part  of  the  nasal  septum  (see  p.  148).  As  development  pro- 
ceeds, the  epithelium  (ectoderm)  of  the  nasal  fossae  grows  still  deeper  into  the 
subjacent  mesoderm,  the  fossse  thus  becoming  converted  into  the  nasal  sacs, 
which  lie  above  the  oral  cavity.  According  to  Hochstetter  and  Peter,  the 


580  TEXT-BOOK  OF  EMBRYOLOGY. 

nasal  sacs  are  not  at  first  in  communication  with  the  oral  cavity,  but  lie  above, 
and  are  separated  from  it  by  a  plate  of  tissue  which  gradually  becomes  thinned 
out  along  the  deeper  part  of  the  sacs  to  form  the  bucco-nasal  membrane  (Hoch- 
stetter).  Later  (in  embryos  of  15  mm.),  the  bucco-nasal  membrane  ruptures 
and  the  deep  ends  of  the  sacs  thus  come  to  open  into  the  mouth  cavity,  the 
openings  being  known  as  the  primitive  choanen.  In  front  of  the  primitive 
choanen,  the  nasal  passages  (formerly  the  nasal  sacs)  are  separated  from 
the  mouth  cavity  by  a  plate  of  tissue,  known  as  the  primitive  palate  (Fig.  509). 
The  latter  is  produced  by  the  fusion  of  the  maxillary  process  with  the  lateral 
and  medial  nasal  processes  (see  p.  148),  the  outer  nares  thus  being  somewhat 
separated  from  the  border  of  the  mouth. 

The  further  separation  of  the  nasal  passages  from  the  oval  cavity  has  been 
described  in  connection  with  the  development  of  the  mouth  (p.  317)  and  the 


Lateral  nasal  process 

Outer  nasal  opening 

Maxillary  process 

Eye 

Primitive  choanen 

Palatine  process 


FIG.  509. — From  a  model  of  the  anterior  part  of  the  head  of  a  15  mm.  human  embryo.     The  lower 
jaws  (mandibular  processes)  have  been  removed.     Peter. 

development  of  the  palatine  processes  of  the  maxillae.  It  may  be  repeated 
briefly,  however,  that  from  each  maxillary  process  a  horizontal  extension  grows 
across  between  the  oral  and  nasal  cavities  until  it  meets  and  fuses  with  its  fellow 
of  the  opposite  side  and  with  the  nasal  septum  in  the  medial  line,  thus  forming 
the  palate  which  is  continuous  with  the  primitive  palate  mentioned  above. 
(See  Figs.  178  and  510.)  In  this  way  the  nasal  cavities  or  chambers  become 
separated  from  the  oral  cavity,  but  remain  in  communication  with  the  pharyn- 
geal  cavity  through  the  posterior  nares. 

The  nasal  cavities  increase  enormously  in  size  and  the  epithelial  surface  in 
extent,  owing  to  (i)  the  formation  of  the  palate  alluded  to  above,  (2)  the  develop- 
ment of  the  nasal  concha  which  has  been  described  on  page  192,  and  (3)  the 
development  of  accessory  cavities — maxillary,  frontal  and  sphenoidal  sinuses, 
which  represent  evaginations,  so  to  speak,  from  the  nasal  cavities. 

Probably  correlated  with  the  above-mentioned  increase  in  extent  of  the 
nasal  chambers  is  the  fact  that  in  lung-breathing  Vertebrates  the  chambers 


THE  ORGANS   OF  SPECIAL  SENSE. 


581 


have  acquired  a  secondary  function.  In  these  forms  the  nose  is  not  only  an 
apparatus  for  receiving  olfactory  stimuli,  but  also  serves  to  convey  air  to  and 
from  the  lungs;  it  is  in  a  sense' a  respiratory  atrium.  The  sensory  epithelium 
which  the  olfactory  nerves  supply  is  limited  to  relatively  small  areas  in  the  supe- 
rior conchae  and  nasal  septum.  Stratified  columnar  ciliated  epithelium  lines  all 
other  parts  of  the  cavities. 

Studies  on  the  development  of  the  olfactory  nerve  have  led  to  diverse 
opinions,  but  the  investigations  of  His  and  Disse  go  to  show  that  the  fibers 
are  processes  of  cells  derived  from  the  thickened  ectoderm  or  olfactory  placodes. 
In  human  embryos  of  about  four  weeks  some  of  the  cells  in  the  upper  part  of 
the  nasal  fossa  become  modified  to  form  the  neuro-epithelium.  From  the 


Jacobson's  organ 
Inferior  concha 

Jacobson's  cartilage 


Palatine  process 


Nasal  septum 


Nasal  cavity 


Oral  cavity 


FIG.  510. — From  a  section  through  the  head  of  a  human  embryo  of  28  mm.,  showing  the  nasal 
septum,  the  nasal  cavities,  the  oral  cavity,  and  the  palatine  processes.     Peter. 

peripheral  pole  of  each  cell  a  short  slender  process  grows  out  to  the  surface  of 
the  epithelium.  From  the  opposite  pole  a  slender  process  (the  axone)  grows 
centrally  until  it  penetrates  the  olfactory  lobe,  where  it  ends  in  contact  with  the 
dendrites  of  the  first  central  neurone  of  the  olfactory  tract.  Most  of  these  cells 
remain  in  the  epithelial  layer,  but  a  few  wander  into  the  subjacent  mesoderm 
and  become  bipolar  cells  which  resemble  the  bipolar  cells  of  the  embryonic 
posterior  root  ganglia  (p.  502).  Other  epithelial  cells  of  the  nasal  fossa  are 
converted  into  the  sustentacular  cells  of  the  olfactory  areas. 

Jacobson's  organ  arises  at  the  beginning  of  the  third  month  as  a  small  out- 
pocketing  of  the  epithelium  on  the  lower  anterior  part  of  the  nasal  septum 
(Fig.  510).  This  evagination  grows  backward  as  a  slender  sac  along  the  nasal 
septum  for  a  distance  of  several  millimeters  and  ends  blindly.  In  the  adult 
the  sac  degenerates  and  often  disappears.  In  some  of  the  lower  Mammals 


582  TEXT-BOOK  OF  EMBRYOLOGY. 

Jacobson's  organ  develops  to  a  greater  degree,  and  some  of  the  epithelial  cells 
send  out  processes  which  pass  to  the  olfactory  lobes. 

THE  EAR. 

The  ear  of  higher  Vertebrates  consists  of  three  parts — the  internal,  middle, 
and  external.  Of  these,  the  internal  is  the  sensory  portion  proper  and,  so  far 
as  the  epithelial  elements  are  concerned,  is  of  ectodermal  origin,  but  secondari!? 
becomes  embedded  in  the  subjacent  mesoderm.  It  constitutes  a  complicated 
and  highly  specialized  structure  for  the  reception  of  certain  stimuli  that  are  to  be 
conveyed  to  the  central  nervous  system.  From  a  functional  standpoint  it  may 
be  divided  into  the  portion  composed  of  the  semicircular  canals  and  their  ap- 
pendages, which  is  concerned  in  receiving  and  transmitting  stimuli  destined 

Rh.  br. 

End.  ap. 
Aud.  ves. 


Co.  gang. 


FIG.  511. — Half  of  a  transverse  section  through  the  region  of  the  developing  ear  of  a  sheep 

embryo  of  13  mm.     Bottcher. 

Aud.  ves.,  Auditory  vesicle;  Co.   gang.,    cochlear  ganglion;  End.  ap.,  endolymphatic 
appendage;  Rh.br.,  rhombic  brain. 

for  the  static  and  equilibration  centers  in  the  central  nervous  system,  and  the 
cochlear  portion,  which  is  concerned  in  receiving  and  transmitting  auditory 
stimuli.  The  middle  and  outer  ear  represent  modified  portions  of  the  most 
cranial  of  the  branchial  arches  and  grooves,  and  constitute  an  apparatus  for 
conducting  sound  waves  to  the  cochlear  portion  of  the  inner  ear. 

The  Inner  Ear. — In  embryos  of  2  to  4  mm.,  the  ectoderm  becomes  some- 
what thickened  over  a  small  area  lateral  to  the  still  open  neural  groove  in  the 
region  of  the  future  hind-brain.  This  thickening  is  often  spoken  of  as  the 
auditory  placode  (see  p.  499).  Owing  to  more  rapid  growth  of  the  cells  in  the 
deeper  layers  of  the  placode,  it  soon  becomes  converted  into  a  cup-shaped 
depression  which  is  known  as  the  auditory  pit.  The  edges  of  the  pit  fold 
in  and  fuse  and  the  pit  thus  becomes  the  auditory  vesicle  (otocyst),  which 
finally  becomes  constricted  from  the  parent  ectoderm  and  lies  free  in  the  sub- 
jacent mesoderm  (Fig.  511). 


THE   ORGANS   OF  SPECIAL  SENSE.  583 

At  this  stage  (embryos  of  4  to  5  mm.)  the  auditory  vesicle  is  an  oval  or 
spherical  sac  the  wall  of  which  consists  of  two  or  three  layers  of  undifferen- 
tiated  epithelial  cells.  It  lies  against  the  neural  tube  and  is  connected  with  the 
latter  by  the  acoustic  ganglion  (Fig.  512,  a).  About  the  same  time  an  evagina- 
tion  appears  on  the  dorsal  side  of  the  auditory  vesicle,  forming  the  anlage  of  the 
endolymphatic  appendage  (Fig.  512,  a,  b,  c).  The  evagination  continues  to 
elongate  and  comes  to  form  a  club-shaped  structure,  the  distal  end  of  which 
becomes  flattened  to  form  the  endolymphatic  sac,  the  narrower  proximal  portion 
constituting  the  endolymphatic  duct  (Fig.  512  a-ri).  The  epithelium,  which  at 
first  consisted  of  two  or  three  layers  of  cells,  becomes  reduced  to  a  single  layer. 
In  the  chick  the  endolymphatic  appendage  is  formed  out  of  the  original  union 
between  the  ectoderm  and  the  auditory  vesicle  (Keibel,  Krause).  In  Reptiles 
and  Amphibia  (Peter,  Krause)  and  in  man  (Streeter),  on  the  other  hand,  this 
appendage  develops  independently  of  the  union,  appearing  on  the  dorsal  side  of 
the  seam  of  closure  in  the  auditory  vesicle. 

In  embryos  of  about  6  mm.  the  auditory  vesicle  (apart  from  the  endolymph- 
atic appendage)  becomes  differentiated  into  two  portions  or  pouches — a  bulging, 
triangular  one  above,  which  is  connected  with  the  endolymphatic  appendage, 
and  a  more  flattened  one  below.  The  former  is  the  vestibular  pouch,  the  latter 
the  cochlear  pouch  (Fig.  512,  b-f).  Between  the  two  is  a  portion  of  the  vesicle 
which  is  destined  to  give  rise  to  the  saccule  and  utricle,  and  which  may  be  called 
the  atrium  (Streeter).  Properly  speaking,  the  atrium  is  a  division  of  the 
vestibular  pouch.  The  cochlear  pouch  is  phylogenetically  a  secondary  diver- 
ticulum  which  develops  from  the  atrium,  appearing  first  in  the  lowest  land- 
inhabiting  Vertebrates  (Amphibia). 

As  mentioned  above,  the  vestibular  pouch  early  assumes  the  form  of  a 
triangle,  with  the  apex  toward  the  endolymphatic  appendage.  The  three 
borders  of  the  triangle  form  the  anlagenrof  the  semicircular  canals  and  bear  the 
same  interrelation  as  the  latter.  At  the  same  time  a  vertical  groove  (the  lateral 
groove)  appears  between  the  anlage  of  the  posterior  canal  and  the  posterior  end 
of  the  lateral  canal  (Fig.  512,  b,  d). 

The  formation  of  the  semicircular  canals  is  shown  in  Fig.  512,  g-k.  The 
edges  of  the  triangular  vestibular  pouch  expand  and  become  more  or  less 
crescentic  in  shape.  The  two  walls  in  the  concavity  of  each  crescent  come 
together  and  then  break  away  (Fig.  512,  g,  j,  absorp.focus),  thus  leaving  the  rim 
of  the  crescent  as  a  canal  attached  at  its  two  ends  to  the  utricle.  The  breaking 
away  affects  first  the  superior,  then  the  posterior,  and  finally  the  lateral  canal. 
During  these  gross  changes  the  epithelium  becomes  reduced  to  a  single  layer 
of  cells. 

At  one  end  of  each  canal  an  enlargement  appears  to  form  the  ampulla,  as 
shown  in  Fig.  512,  /,  m,  n,  and  Fig.  513,  a,  b,  c. 


584 


TEXT-BOOK  OF  EMBRYOLOGY. 


THE  ORGANS  OF  SPECIAL  SENSE. 


585 


586  TEXT-BOOK  OF  EMBRYOLOGY. 

The  utricle  and  saccule  represent  divisions  of  the  portion  of  the  vestibular  sac 
which  is  known  as  the  atrium,  and  into  which  the  endolymphatic  appendage 
and  cochlea  open  (see  p.  583) .  In  embryos  of  about  20  mm.  a  horizontal  con- 
striction begins  to  divide  the  atrium  into  an  upper  utricular  portion,  into  which 
the  semicircular  canals  open,  and  a  lower  saccular  portion  (Fig.  512,  /,  m). 
The  constriction  begins  on  the  side  opposite  the  endolymphatic  appendage  and 
gradually  extends  across  the  atrium  until  it  finally  divides  the  opening  of  the 
endolymphatic  appendage  into  two  parts  (Fig.  513,  a,  b,  c).  One  of  these 
parts  opens  into  the  utricle,  the  other  into  the  saccule,  the  two  parts  together 
constituting  the  utriculo  saccular  duct. 

As  stated  before-,-  the  two-  or  three-layered  epithelium  of  the  earlier  stages 
becomes  reduced  to  a  single  layer.  The  cells  of  this  layer  are  low  cuboidal, 
with  the  exception  of  those  over  small  areas  in  the  ampullae,  in  the  saccule,  and 
in  the  utricle.  Over  an  elongated  area  in  each  ampulla  (crista  ampullaris),  a 
round  area  in  the  saccule  and  another  in  the  utricle  (macula  acustica),  the 
epithelium  becomes  high  columnar,  some  of  the  cells  developing  cilia  on  their 
free  borders  ("hair  cells,"  neuro-epithelium) ,  the  others  becoming  the  susten- 
tacular  cells.  These  areas  are  the  end-organs  of  the  vestibular  nerve  (see  p.  499) . 

As  already  mentioned,  the  cochlear  pouch  appears  as  an  outgrowth  from  the 
lower  side  of  the  atrium  (see  also  Fig.  512,  b-f) .  The  pouch  becomes  somewhat 
flattened,  and,  as  it  continues  to  grow  in  length,  becomes  coiled  like  a  snail- 
shell  (Fig.  512,  g-n;  Fig.  513,  a-c).  This  first  formed  coiled  structure  is  the 
cochlear  duct,  or  scala  media.  At  the  same  time,  it  becomes  distinctly  marked 
off  from  the  lower  part  of  the  atrium  (now  the  saccule)  by  a  constriction,  the 
constricted  portion  forming  the  ductus  reuniens  (Fig.  512,  l-n;  Fig  513,  a-c). 

All  the  structures  thus  far  considered  are  at  first  closely  invested  by  meso- 
derm.  Later,  this  portion  of  the  mesoderm  gives  rise  to  special  tissues,  and,  in 
the  region  of  the  cochlear  duct,  to  the  scala  vestibuli  and  scala  tympani.  The 
cells  immediately  around  the  vesicle  proliferate  and  a  dense  fibrous  layer  is 
formed;  outside  of  this  fibrous  layer  the  tissue  becomes  gelatinous;  outside  of 
this  again  another  fibrous  layer  is  formed,  around  which  cartilage  develops. 
The  inner  fibrous  layer  gives  rise  to  the  connective  tissue  that  supports  the 
epithelial  lining  of  the  vesicle.  The  gelatinous  layer  degenerates  to  form  a 
fluid  known  as  the  peritymfb,  the  space  containing  the  fluid  being  the  perilymph- 
atic  space.  The  outer  fibrous  layer  becomes  the  perichondrium — later  the 
periosteum  when  the  cartilage  is  replaced  by  the  petrous  portion  of  the  tem- 
poral bone. 

In  the  cochlear  region  the  conditions  are  somewhat  modified.  Here  the 
gelatinous  layer  does  not  form  a  complete  covering  for  the  cochlear  duct,  but  is 
interrupted  along  two  lines,  (i)  Laterally  the  fibrous  layer  lying  next  the 
cochlear  duct  is  fused  with  the  perichondrium  (outer  fibrous  layer)  (Fig.  514). 


THE  ORGANS  OF  SPECIAL  SENSE. 


587 


(2)  Medially  the  inner  fibrous  layer  is  fused  with  the  perichondrium  of  a  shelf-like 
process  of  cartilage  which  later  ossifies  to  form  the  bony  spiral  lamina  (Fig. 
514).  By  these  two  partitions,  the  cochlear  perilymphatic  space  is  separated 
into  two  spiral  compartments  which  communicate  only  at  the  apex  of  the 
cochlea.  The  larger  of  these  compartments,  the  scala  vestibuli,  communicates 
with  the  perilymphatic  space  around  the  utricle  and  saccule.  The  wall  separat- 
ing the  scala  vestibuli  and  cochlear  duct  becomes  thinned  out  to  form  the 


Cochlear  duct 


Cartilage 

Scala  vestibuli 
(gelatinous  tissue) 


Cochlear  duct 

Cochlear  (spiral)  ganglion 

Coch.  nerve  to  organ  of  Corti 

Scala  tympani 

Cochlear  nerve 

Fibrous  con.  tis. 

Connective  tissue  _| 

Scala  vestibuli 
Perichondrium 

Vestibular  membrane    I| 
Lat.  wall  of  coch.  duct     fe? 

Organ  of  Corti  _  'f 


Scala  tympani  j 


Cartilage 


FIG.  514 — Section  through  the  developing  cochlea  of  a  90  mm.  cat  embryo.     Bottcher. 


vestibidar  membrane  (of  Reissner).  The  smaller  compartment,  the  scala 
tympani,  remains  separated  from  the  cavity  of  the  middle  ear  by  a  thin  mem- 
brane which  closes  the  fenestra  cochlea  (rotunda).  In  the  wall  between  the 
scala  tympani  and  the  cochlear  duct  the  organ  of  Corti  develops  (see  below). 
A  membrane,  similar  to  that  closing  the  fenestra  cochleae,  occurs  between  the 
cavity  of  the  middle  ear  and  the  utricle,  closing  the  fenestra  vestibuli  (ovalis) . 
As  alluded  to  above,  the  organ  of  Corti  develops  from  the  wall  of  the  cochlear 


588  TEXT-BOOK  OF  EMBRYOLOGY. 

* 

duct  between  the  latter  and  the  scala  tympani  (Fig.  514).  The  epithelial  cells 
of  the  cochlear  duct  in  this  region  become  high  columnar  and  arranged  in  two 
ridges  which  extend  throughout  the  entire  length  of  the  duct.  The  cells  of  the 
ridge  nearer  the  axis  of  the  cochlea  give  rise  to  the  membrana  tectoria.  Whether 
this  is  accomplished  by  cuticular  secretion  of  the  cells  or  by  the  fusion  of  long 
hair-like  processes  that  grow  from  their  free  borders  is  not  known.  The  cells  of 
the  outer  ridge  become  differentiated  into  four  groups.  Those  of  the  outer 
group  (next  the  cells  that  give  rise  to  the  membrana  tectoria)  develop  into  the 
inner  hair  cells;  those  of  the  next  group  form  the  pillar  cells;  those  of  the  third 
group  differentiate  into  the  outer  hair  cells;  and  those  of  the  fourth  (outer) 
group  give  rise  to  Hensen's  cells.  The  hair  cells,  as  the  name  indicates,  develop 
delicate  hair-like  processes  on  their  free  borders,  and,  since  the  peripheral 
processes  of  the  spiral  (cochlear)  ganglion  cells  end  around  them,  are  con- 
sidered as  the  sensory  cells  of  the  cochlea,  or  auditory  receptors  (see  p.  499). 

THE  ACOUSTIC  NERVE. — The  acoustic  ganglionic  mass  is  at  first  closely 
associated  with  the  geniculate  ganglion  (ganglion  of  the  facial  (VII)  nerve) ,  the 
two  together  often  being  spoken  of  as  the  acustico-facialis  ganglion  (see  also 
p.  508).  This  lies  in  close  contact  with  the  anterior  wall  of  the  auditory  vesicle 
when  the  latter  is  first  constricted  from  the  ectoderm.  The  origin  of  the  gang- 
lion has  not  been  traced  in  Mammals,  but  in  cow  embryos  the  geniculate  has 
been  seen  to  be  connected  with  the  ectoderm  at  the  dorsal  end  of  the  first 
branchial  groove  (Froriep).  The  acoustic  ganglion  probably  belongs  to  the 
lateral  line  system  (Kupffer)  (see  also  p.  460). 

Although  the  geniculate  and  acoustic  ganglia  are  at  first  closely  associated, 
each  pursues  an  independent  course  of  development.  The  description  here 
will  be  confined  to  the  acoustic.  As  already  mentioned,  this  lies  in  close  apposi- 
tion to  the  side  of  the  neural  tube  and  the  auditory  vesicle  and  just  anterior  to 
the  latter  (Fig.  512,  a).  At  a  very  early  stage  (embryos  of  6-7  mm.),  the  mass 
shows  a  differentiation  into  two  parts — a  dorsal  one,  the  future  vestibular 
ganglion,  and  a  ventral  one,  the  future  cochlear  (spiral)  ganglion  (Fig.  512,  b,  c). 
The  ganglion  cells  become  bipolar  (see  p.  499),  and,  as  is  peculiar  to  the  cells  of 
the  acoustic  ganglia,  remain  in  this  condition.  One  process  of  each  cell  grows 
centrally  to  form  a  root  fiber  of  the  acoustic  nerve,  which  terminates  in  contact 
with  dendrites  of  neurones  in  certain  nuclei  in  the  central  nervous  system.  The 
fibers  from  the  cells  of  the  vestibular  ganglion  form  the  vestibular  root,  those 
from  the  cells  of  the  cochlear  ganglion  form  the  cochlear  root.  The  other  proc- 
ess grows  peripherally  and  penetrates  the  wall  of  the  auditory  vesicle  to  enter 
into  relation  with  certain  cells  that  differentiate  from  the  epithelial  lining  of  the 
vesicle. 

The  peripheral  processes  of  the  vestibular  ganglion  cells  come  into  relation 
with  specialized  cells  (hair  cells)  in  the  ampullae  of  the  semicircular  canals 


THE   ORGANS   OF  SPECIAL  SENSE.  589 

(crista  ampullaris)  and  in  the  saccule  and  utricle  (macula  acustica)  (see 
p.  586) .  The  nerve  itself  becomes  divided  into  certain  branches,  as  indicated 
in  the  following  table  (Streeter}.  The  peripheral  terminations  of  the  various 
branches  are  indicated  in  parentheses.  Compare  with  Fig.  512,  /,  m,  n,  and 
Fig.  513,  a,  b,  c. 

ramus  ampul,  sup.  (crista  ampul.) 


pars  superior 


ramus  ampul,  ext.  (crista  ampul.) 


ramus  recess,  utric.  (macula  acust.) 
N.  vestibularis       ] 

J  ramus  saccul.  (macula  acust.) 
[  pars  inferior     |  ramus  ampul,  (crista  ampul.) 

The  vestibular  ganglion  cells,  instead  of  remaining  in  a  compact  mass,  come 
to  form  two  fairly  distinct  masses  in  the  course  of  the  nerve  (Fig.  513,  0,  b,  c). 
One  of  these  apparently  is  connected  with  the  pars  inferior,  the  other  with  the 
pars  superior. 

The  cochlear  ganglion  cells  at  an  early  stage  become  closely  associated  with 
the  developing  cochlear  duct  and,  as  the  latter  forms  a  spiral,  are  carried"  along 
with  it.  They  thus  come  to  form  an  elongated  group  of  cells  extending  through- 
out the  entire  length  of  the  cochlea  (whence  the  name,  spiral  ganglion)  (Fig. 
512,  j-n;  Fig.  513,  a-c).  Consequently,  the  peripheral  processes  of  these  cells, 
which  terminate  in  connection  with  the  hair  cells  of  the  organ  of  Corti,  are  com- 
paratively short.  The  central  processes  are  naturally  longer  and  form  the 
cochlear  nerve  root  which  is  twisted  like  a  rope  in  part  of  its  course  (Fig.  513,  c). 

The  Middle  Ear. — The  cavity  of  the  middle  ear  develops  from  the  upper 
(dorsal)  part  of  the  first  inner  branchial  groove.  The  epithelial  lining  of  the 
cavity  is  thus  of  course  derived  from  entoderm,  and  the  other  structures 
(auditory  ossicles,  etc.)  from  the  adjacent  mesoderm. 

It  has  been  stated  elsewhere  that  the  mesoderm  in  the  first  and  second 
branchial  arches  gives  rise,  among  other  things,  to  certain  skeletal  elements. 
In  the  first  arch  there  develops  a  rod  of  cartilage,  known  as  Meckel's  cartilage, 
which  extends  from  the  symphysis  of  the  lower  jaws  to  the  region  of  the  upper 
part  of  the  first  inner  branchial  groove  (p.  196;  Figs.  174,  177,  180).  The 
proximal  end  of  the  cartilage  becomes  constricted  to  form  two  masses  which 
constitute  the  anlagen  of  the  malleus  and  incus  (Figs.  173  and  174).  In  the 
second  arch  there  develops  a  rod  of  cartilage  which  forms  the  lesser  horn  of  the 
hyoid  bone,  the  stylohyoid  ligament,  and  the  styloid  process  (Figs.  174,  177, 
1 80) .  In  close  relation  to  the  dorsal  end  of  the  styloid  process,  in  the  mesoderm 
destined  to  give  rise  to  the  periotic  capsule,  a  mass  of  cartilage  appears  which 
is  destined  to  give  rise  to  the  stapes  (except  the  base  ?) .  It  has  not  been  fully 
determined  whether  the  stapes  is  actually  a  derivative  of  the  cartilage  of  the 
second  arch  or  of  the  mesenchyme  near  its  dorsal  end.  It  has  been  suggested 


590  TEXT-BOOK  OF  EMBRYOLOGY. 

that  the  base  of  the  stapes  is  of  intramembranous  origin  and  that  the  rest  of  the 
bone  is  derived  from  the  cartilage  of  the  second  arch.  Its  close  association 
with  the  cartilage  of  the  second  arch  possibly  indicates  its  phylogenetic  origin 
from  the  latter. 

At  first  the  auditory  ossicles  are  embedded  in  the  mesoderm  dorsal  to  the 
first  inner  branchial  groove,  that  is,  dorsal  to  the  cavity  of  the  middle  ear.  As 
development  proceeds,  the  mesoderm  is  converted  into  a  spongy  tissue  which 
finally  degenerates.  At  the  same  time  the  ear  cavity  enlarges  and  wraps  itself, 
as  it  were,  around  the  ossicles.  The  latter  thus  come  to  lie  within  the  cavity 
of  the  tympanum,  but  are  covered  by  a  layer  of  epithelium  (entoderm)  which 
is  continuous  with  that  lining  the  cavity. 

Toward  the  end  of  fcetal  life,  outgrowths  from  the  cavity  of  the  tympanum 
begin  to  invade  the  temporal  bone.  This  process  continues  for  some  time 
after  birth  and  results  in  the  formation  of  cavities  within  the  mastoid  part  of 
the  temporal  bone.  These  cavities  are  the  mastoid  cells,  the  epithelial  lining 
of  which  is  continuous  with  that  of  the  tympanic  cavity. 

The  Eustachian  tube  represents  the  lower  (ventral)  portion  of  the  diver- 
ticulum  which  forms  the  cavity  of  the  tympanum.  In  other  wrords,  as  the 
dorsal  part  of  the  first  inner  branchial  groove  enlarges  to  form  the  cavity  of  the 
middle  ear,  the  narrow  part  of  the  groove,  just  ventral  to  the  cavity,  persists 
as  a  communication  between  the  latter  and  the  pharynx. 

The  Outer  Ear. — The  outer  ear  is  formed  from  the  dorsal  part  of  the  first 
outer  branchial  groove  and  the  adjacent  portions  of  the  first  and  second  arches 
(see  Fig.  123).  The  ventral  part  of  the  groove  flattens  out  and  disappears. 
The  dorsal  part  becomes  deeper  to  form  a  funnel-shaped  depression  (during 
the  second  month;  Fig.  126).  From  the  deeper  part  of  the  funnel  a  solid  mass 
of  ectoderm  grows  inward  until  it  comes  into  relation  with  the  mesoderm  im- 
mediately around  the  developing  cavity  of  the  tympanum,  or,  more  specifically, 
the  mesoderm  surrounding  the  handle  of  the  malleus.  Here  it  spreads  out 
into  a  disk-like  mass.  About  the  seventh  month,  the  disk  splits  into  two  layers. 
The  inner  layer,  which  is  separated  from  the  epithelium  of  the  middle  ear  by  a 
thin  sheet  of  mesoderm,  becomes  the  outer  layer  of  the  tympanum.  The 
tympanum  is  thus  composed  of  an  inner  (entodermal)  and  an  outer  (ectoder- 
mal)  layer,  with  a  small  amount  of  mesoderm  between.  From  its  mode  of 
development,  the  tympanum  may  be  considered  in  a  sense  as  the  wall  which 
separates  the  first  inner  from  the  first  outer  branchial  groove. 

The  split  in  the  ectodermal  disk  (see  above)  gradually  extends  outward, 
invading  the  solid  ectodermal  invagination  until  it  finally  unites  with  the 
bottom  of  the  funnel-shaped  depression  on  the  surface,  thus  forming  the 
external  auditory  meatus. 

The  external  ear  for  auricle)  is  derived  from  the  portions  of  the  first  and 


THE  ORGANS   OF  SPECIAL  SENSE. 


591 


second  branchial  arches  surrounding  the  dorsal  part  of  the  first  outer  branchial 
groove  (see  Figs,  122,  123,  126,  127).  About  the  end  of  the  fourth  week,  the 
caudal  border  of  the  first  arch  exhibits  three  small  elevations  or  tubercles 
(Fig.  515,  A,  1-3),  the  cranial  border  of  the  second  arch  the  same  number  (Fig. 
515,  A,  4-6).  A  groove,  extending  down  the  middle  of  the  second  arch,  marks 
off  a  ridge  (c)  lying  caudal  to  the  three  tubercles.  The  ventral  tubercle  (i)  of 
the  first  arch  gives  rise  to  the  tragus.  The  middle  tubercle  (5)  of  the  second  arch 


\ 


_r 


FIG.  515. — Stages  in  the  development  of  the  external  ear  (auricle).  A,  Embryo  of  n  mm.;  By  of 
13.6  mm.;  C,  of  15  mm.;  D,  foetus  at  the  beginning  of  the  3d  month;  E,  foetus  of  8.5  cm.; 
F,  fcetus  at  term.  For  explanation  of  numerals,  see  text.  His,  McMurrich. 

develops  into  the  antitragus.  The  middle  and  dorsal  tubercles  (2  and  3)  of 
the  first  arch  unite  with  the  ridge  (c)  on  the  second  arch  to  form  the  helix. 
The  dorsal  tubercle  (4)  of  the  second  arch  gives  rise  to  theanthelix.  The 
ventral  tubercle  (6)  of  the  second  arch  produces  the  lobule.  It  should  be  noted 
that  in  the  third  month  the  dorsal  and  caudal  portions  of  the  helix  are  bent 
forward  and  conceal  the  anthelix. 

Anomalies. 

Malformations  of  the  nose  have  been  alluded  to  in  connection  with  hare  lip, 
cleft  palate,  etc.,  on  page  212,  and  are  also  discussed  in  the  chapter  on  tera- 
togenesis  (XIX) .  Malformations  affecting  the  eye  (cyclopia,  microphthalmia, 
etc.)  and  the  ear  (synotia,  etc.)  are  dealt  with  in  the  chapter  on  teratogenesis. 


592  TEXT-BOOK  OF  EMBRYOLOGY. 

References  for  Further  Study. 
THE  EYE. 

GALLENGA:  Entwickelung  des  Auges.  Encyklopddie  der  Augenheilkunde,  Lief.  6  and  7, 
1902. 

HOLDEN:  An  Outline  of  the  Embryology  of  the  Eye,  New  York,  1893. 

VON  KOLLIKER:  Die  Entwicklung  und  Bedeutung  des  Glaskorpers.  Zeitschr.  fur 
•wissensch.  Zoolog.,  Bd.  LXVI,  1904. 

LANGE,  O.:  Einblicke  in  die  embryonale  Anatomic  und  Entwicklung  des  Menschen- 
auges.  1908. 

RABL,  C.:  Ueber  den  Bau  und  Entwickelung  der  Linse.  Zeitschr.  fur  wissensch.  ZooL, 
Bd.  LXII  and  LXV,  1898;  LXVII,  1899. 

RAYMON  Y  CAJAL.:  Nouvelles  contributions  a  1'etude  histologique  de  la  re'tine.  Jour,  de 
VAnat.  et  de  la  PhysioL,  Vol.  XXXII,  1896. 

ROBINSON.  A.:  On  the  Formation  and  Structure  of  the  Optic  Nerve  and  its  Relation  to 
the  Optic  Stalk.  Jour,  of  Anat.  and  Physiol.,  Vol.  XXX,  1896. 

VON  SPEE:   Recherches  sur  Porigine  du  corps  vitre.    Arch,  de  Biol.,  Vol.  XIX,  1902. 

THE  NOSE. 

BEARD,  J.:  Morphological  Studies.  The  Nose  and  Jacobson's  Organ.  Zool.  Jahrbuch, 
Bd.  Ill,  1889. 

DISSE,  J.:  Die  erste  Entwickelung  der  Riechnerven.     Anat.  Hefte,  Bd.  IX,  1897. 

His,  W.:  Beobachtungen  zur  Geschichte  der  Nasen-  und  Gaumenbildung  beim 
menschlichen  Embryo.  AbhandL  d.  math.-phys.  Klasse  Ko'nig.  Sachs.  Gesellsch.  d. 
Wissensch.,  1901. 

HOCHSTETTER,  F.°.  Ueber  die  Bildung  der  primitiven  Choanen  beim  Menschen.  Ver' 
handl.  d.  anat.  Gesellsch.,  Bd.  VI,  1892. 

VON  MIHALKOWICZ,  V.:  Nasenhohle  und  Jacobsonsches  Organ.  Eine  morphologische 
Studie.  Anat.  Hefte,  Bd.  XI,  1898. 

PETER,  K.:  Die  Entwickelung  des  Geruchsorgans  und  Jacobson'schen  Organs  in  der 
Reihe  der  Wirbeltiere.  In  Hertwig's  Handbuch  d.  vergleich.  u.  experiment.  Entwickel- 
ungslehre  d.  Wirbeltiere,  Bd.  II,  Teil  II,  1901. 

THE  EAR. 

BAGINSKY,  B.:  Zur  Entwickelung  der  Gehorschnecke.  Arch.f.  mik.  Anat.,  Bd.  XXVIII, 
1886. 

BOETTCHER,  A.:  Ueber  Entwickelung  und  Bau  des  Gehorlabyrinths.  Verhandl.  d. 
Kais.Leop. -Carol.  Akad.,  Bd.  XXXV,  1869. 

BROMAN,  I.:  Die  Entwickelungsgeschichte  der  Gehorknochelchen  beim  Menschen. 
Anat.  Hefte,  Bd.  XI,  1898. 

FUCHS,  H.:  Bemerkungen  iiber  die  Herkunft  und  Entwickelung  der  Gehorknochelchen 
bei  Kaninchen-Embryonen.  Arch.f.  Anat.  u.  Phys.,  Anat.  Abth., SuppL,  1905. 

HENSEN,  V.:    Zur  Morphologic  der  Schnecke.  Zeitschr.  f.  wissensch.  ZooL,  Bd.  XIII,  1863 

His,  W.:  Zur  Entwickelung  des  Acusticofacialisgebiets  beim  Menschen.  Arch.f.  Anat. 
u.  Phys.,  Anat.  Abth.,  SuppL,  1899. 

KRAUSE,  R.:  Entwickelungsgeschichte  des  Gehororgans.  In  Hertwig's  Handbuch  d. 
vergleich.  u.  experiment.  Entwickelungslehre  d.  Wirbeltiere,  Bd.  II,  Teil  II,  1902. 

STREETER,  G.  L.:  On  the  Development  of  the  Membranous  Labyrinth  and  the  Acoustic 
and  Facial  Nerves  in  the  Human  Embryo.  Am.  Jour,  of  Anat.,  Vol.  VI,  No.  2,  1907. 


CHAPTER  XIX. 

TERATOGENESIS. 

MALFORMATIONS  INVOLVING  MORE  THAN  ONE  INDIVIDUAL. 
Classification,  Description,  Origin. 

To  give  a  complete  list  of  the  numerous  malformations  in  man,  even  of 
those  which  affect  the  external  form  of  the  body,  is  obviously  beyond  the  scope 
of  this  book.  In  this  chapter  it  is  the  purpose  of  the  writers  merely  to  describe 
in  a  general  way  the  most  striking  malformations  and  discuss  briefly  the  causes 
underlying  the  origin  of  malformations.  For  further  details  concerning  the 
subject  the  student's  attention  is  directed  to  "References  for  Further  Study" 


The  classification  of  malformations  is  attended  by  great  difficulties.  This 
is  due  mainly  to  the  fact  that  their  complexities  are  not  wholly  understood.  It 
is  due  also  in  a  measure  to  the  fact  that,  apart  from  certain  malformations 
which  always  occur  in  like  manner  in  different  individuals,  there  are  so  many 
irregularities  and  deviations  from  any  type  that  might  arbitrarily  be  chosen. 
The  classification  made  by  St.  Hilaire  three-quarters  of  a  century  ago, 
although  apparently  complete,  showed  many  incongruities  as  teratology 
became  more  firmly  established  upon  an  embryological  basis.  Later 
Bischoff  formulated  a  division  based  upon  the  embryological  significance 
of  malformations.  This  in  turn  was  elaborated  by  Forster,  and  Forster's 
scheme  has  been  adopted  by  Marchand  and  others.  As  knowledge  concern- 
ing teratogenesis  is  added  to,  it  may  be  that  further  changes  in  classification  will 
be  necessary,  especially  in  view  of  the  fact  that  much  light  is  being  thrown  by 
experimental  methods  upon  the  origin  of  malformations. 

Marchand's  scheme  of  duplicate  monsters  is  given  here  as  a  convenient  one 
for  a  comprehensive  view  of  anomalous  conditions  affecting  two  individuals. 
I.  Both  bodies  derived  from  anlagen  which  developed  from  one  ovum 
and   which    were   originally  similar   and   symmetrical:    Symmetrical 
duplicity. 
A.  Both  bodies  originally  complete  :    Complete  duplicity. 

i.  The  two  bodies  remain  separate;  union  confined  to  chorion: 
Twins;  free  duplicities. 

a.  Both  bodies  formed  alike,  each  capable  of  living:   Equal 
monochorionic  twins. 
593 


594  TEXT-BOOK  OF  EMBRYOLOGY. 

b.  One  body  normal,  the  other  abnormal  or  much  mal- 
formed:    Unequal  monochorionic  twins. 

2.  The  two  bodies  united;  formed  alike  (equal),  or  one  remains 
more  or  less  rudimentary  (unequal) :  Twins  joined  together; 
duplicate  monsters. 

a.  Union  confined  to  lower  end  of  body:     Double  monsters 
with  posterior  union;  anterior  duplicity. 

b.  Union  confined  to  middle  of  body,  or  extending  from 
middle  forward:     Double  monsters  with  middle  union. 

c.  Union  limited  to  upper  end  of  body,  or  extending  from 
upper  end  downward:     Double  monsters  with  anterior 
union;  posterior  duplicity. 

B.  Duplicity  does  not  affect  entire  anlage,  but  only  a  part :   Incomplete 
duplicity. 

1.  Two  incomplete  anlagen  (or  primitive  streaks)  pass  over  into 
a  single  anlage:    Posterior  incomplete  duplicity. 

2.  An  originally  single  anlage  forms  by  dichotomous  growth  two 
separate  upper  (anterior)  ends:  Anterior  incomplete  duplicity. 

In  addition:     Triplicity,  quadruplicity,  etc.,  (multiplicity). 
II.  Both   bodies   derived   from  two  originally  dissimilar,  asymmetrical 
anlagen,  of  which  one,  always  rudimentary,  becomes  more  or  less  en- 
closed and  nourished  by  the  other:  True  parasitic  duplicity;  asym- 
metrical duplicity. 

In  addition:    Teratoid  tumors. 

SYMMETRICAL  DUPLICITY. 

As  seen  from  the  foregoing  scheme,  there  are  included  under  this  head 
double  forms  in  which  both  embryos  develop  within  a  single  chorion  (mono- 
chorionic twins),  and  in  which  the  bodies  may  be  distinct  and  separate 
(complete  duplicity)  or  may  be  united  (incomplete  duplicity).  In  complete 
duplicity  each  embryo  usually  possesses  its  own  amnion  and  umbilical  cord, 
but  both  are  attached  to  the  same  placenta.  In  such  cases  the  conditions  of 
nutrition  and  rate  of  growth  may  be  so  similar  in  the  two  individuals  that  their 
development  is  equal  (equal  monochorionic  twins).  They  may  grow  to 
maturity,  and  they  always  bear  a  remarkable  resemblance  to  each  other  in 
physical  features  and  in  mental  characteristics  and  are  always  of  the  same 
sex.  More  commonly,  however,  the  development  of  separate  monochorionic 
twins  is  unequal,  caused  probably  by  dissimilar  conditions  of  nutrition.  In 
some  instances  the  less  favored  individual  is  but  slightly  affected,  so  that  it 
may  be  born  and  be  able  to  maintain  an  independent  existence.  On  the  other 


TERATOGENESIS.  595 

hand,  the  nutrition  of  one  embryo  may  be  so  seriously  impaired  that  it  dies. 
When  death  occurs  during  the  earlier  months  of  pregnancy  the  dead  embryo 
is  subjected  to  pressure  by  the  living  one  and  is  sometimes  distorted  and 
flattened  into  a  thin  mass  known  as  a  fcetus  papyraceus. 

Equal  growth  of  monochorionic  twins  implies  an  almost  perfect  nutritive 
balance,  since  both  embryos  derive  their  nourishment  from  the  same  placenta. 
Any  condition  that  disturbs  the  nutritive  balance  tends  to  affect  adversely  the 
less  favored  embryo,  so  that  development  does  not  proceed  equally  (unequal 
monochorionic  twins).  One  of  the  first  consequences  of  such  a  disturbance 
may  be  an  impaired  or  arrested  development  of  the  heart,  in  which  case  the 
weaker  embryo  may  become  an  acardiac  monster. 

This  condition  does  not  necessarily  imply  the  absence  of  the  heart  in  the 
affected  twin;  for  it  may  possess  a  functionating  heart,  or  it  may  become  an 
amorphous  mass  of  tissue  which  derives  its  total  blood  supply  through  the 
action  of  the  heart  of  the  stronger  twin,  or  there  may  be  any  form  between  the 
two  extremes.  In  any  case  the  acardiac  monster — acardiacus — receives  its 
blood  wholly  or  in  part  through  the  agency  of  the  stronger  heart. 

Acardia  is  always  accompanied  by  a  so-called  "reversal  of  the  circulation;" 
and  there  are  three  periods  at  which  it  may  originate,  (i)  It  may  originate 
before  the  heart  develops.  As  is  well  known,  the  heart  appears  independently 
of  the  area  vasculosa  and  joins  the  vessels  secondarily  (p.  222).  If,  for  any 
reason,  the  heart  of  one  of  the  embryos  fails  to  develop,  anastomoses  may 
occur  between  the  vascular  anlagen  of  the  two  vascular  areas  and  consequently 
the  normal  embryo  assumes  the  duty  of  nourishing  the  other.  The  latter  be- 
comes an  acardiac  monster.  (2)  It  may  originate  after  the  heart  has  begun  to 
develop,  but  before  the  placental  circulation  is  established.  If,  for  any  reason, 
the  heart  of  one  embryo  should  cease  to  develop  further,  there  would  probably 
be  sufficient  anastomoses  between  the  vitelline  vessels  of  the  two  embryos  to 
enable  the  affected  embryo  to  live  and  become  an  acardiac  parasite.  In  this 
case  no  placental  circulation  would  develop  in  the  parasite.  (3)  Acardia  may 
originate  after  the  establishment  of  the  placental  circulation.  Since  there  is 
but  one  chorion  or  placenta  for  both  embryos  there  is  naturally  a  communica- 
tion between  the  two  circulations  in  the  chorionic  villi.  There  are  also  likely 
to  be  anastomoses  between  the  umbilical  arteries  and  veins.  If,  for  any  reason, 
the  heart  action  of  one  of  the  embryos  should  become  impaired,  there  would  be 
an  influx  of  blood  into  the  vessels  of  that  embryo  owing  to  diminished  pressure. 
Thus  the  blood  from  the  stronger  heart  would  be  pumped  into  the  affected 
embryo  as  well  as  into  the  placenta.  This  blood,  being  impure,  fails  to  nourish 
the  weaker  embryo  properly  and  the  result  is  atrophy  or  degeneration. 

Upon  the  basis  of  other  malformations  that  naturally  accompany  impaired 
development  of  the  heart,  acardiac  monsters  are  divided  into  four  classes. 


596  TEXT-BOOK  OF  EMBRYOLOGY. 

i.  Acardiacicompleti. — The  general  development  of  the  acardiacus  depends  upon 
the  sufficiency  of  the  blood  supply  which  it  receives.  If  there  is  a  well  developed 
anastomosis  between  the  two  placental  circulations  the  weaker  embryo  may 
receive  a  moderately  good  blood  supply  and  develop  into  a  fairly  normal  foetus. 
A  well  formed  trunk  and  head  may  be  present  and  the  extremities  may  be 
represented  in  part  or  in  full.  2.  Acardiaci  acormi. — These  may  possess  only  a 
head,  or  they  may  possess  a  head  and  traces  of  a  trunk  and  extremities. 
Their  evolution  depends  upon  unusual  combinations  of  anastomoses  in  their 
venous  channels.  3.  Acardiaci  acephali. — No  head  is  present.  The  lower 
part  of  the  trunk  is  present,  and  sometimes  other  parts  of  the  trunk.  The  ex- 
tremities may  be  complete,  incomplete  or  absent.  These  forms  are  also  due 
to  peculiar  combinations  of  vascular  anastomoses.  4.  Acardiaci  amor  phi. — As 
the  name  indicates,  there  is  no  typical  form  for  the  affected  embryo.  It  bears  no 
resemblance  to  a  normal  embryo,  but  is  merely  an  irregular  mass  of  tissue. 

In  symmetrical  duplicity,  instead  of  the  two  embryos  in  one  chorion  being 
distinct  and  separate  individuals,  they  may  be  joined  together  to  a  greater  or 
lesser  extent.  The  two  individuals  may  develop  to  practically  the  same 
degree  (equal  united  twins,)  or  one  may  remain  more  or  less  rudimentary 
(unequal  united  twins.)  As  may  be  seen  by  reference  to  the  scheme  on  page  605, 
there  are  three  modes  of  union — posterior,  middle  and  anterior. 

Posterior  Union. — This  may  be  either  dorsal  or  ventral.  In  dorsal  posterior 
union  the  two  bodies  are  joined  together  in  the  pelvic  region,  with  the  dorsal 
surfaces  of  the  twins  directed  toward  each  other.  The  umbilicus  is  double  and 
the  two  umbilical  cords  converge  toward  a  common  placenta — pygopagus. 
The  general  anatomical  features  are  as  follows.  There  is  a  single  coccyx 
and  a  single  sacrum;  pelvic  bones  and  symphyses  are  present  in  normal 
number;  near  the  ends  of  the  large  intestines  the  two  digestive  tubes  unite  to 
form  a  common  lumen,  and  the  two  recta  open  through  a  common  anus  between 
the  more  dorsally  situated  pair  of  extremities;  the  two  spinal  cords  unite  near 
their  lower  ends  to  form  a  single  conus  and  filum  terminale;  the  urogenital 
tracts  are  united  only  to  a  slight  degree.  This  form  of  monster  is  of  interest 
because  it  is  able  to  live  for  years;  indeed  a  number  of  them  have  lived  to 
maturity. 

In  case  of  ventral  posterior  union  the  attachment  may  be  confined  to  the 
pelvic  region  or  may  involve  the  entire  trunk.  In  the  former  instance— 
ischiopagus — the  right  pubic  bone  of  one  pelvis  fuses  with  the  left  pubic  bone 
of  the  other  pelvis,  the  ventral  surfaces  of  the  two  sacra  facing  each  other. 
The  axes  of  the  bodies  may  be  in  line,  or  they  may  form  an  angle.  The  con- 
tinuous ventral  surfaces  of  the  two  bodies  contain  a  single  umbilicus.  The 
organs  in  the  pelvic  region  may  be  single  or  double.  The  lower  extremities 
may  be  fully  developed,  or  there  may  be  only  three,  or  rarely  two.  Sometimes 


TERATOGENESIS.  597 

one  of  the  twins  is  rudimentary,  the  thorax  and  head  being  absent,  but  the 
extremities  present  in  part  (ischiopagus  parasiticus) .  Ischiopagi  seldom 
survive  owing  to  atresia  of  the  anus. 

In  case  the  attachment  extends  along  the  entire  trunk  of  each  twin — • 
ischiothoracopagus — the  two  sacra  are  usually  fused  to  form  a  single  sacrum. 
The  thoraces  of  the  twins  are  joined  by  means  of  a  common  sternum.  The 
upper  extremities  may  all  be  present  (tetrabrachius),  or  there  may  be  three 
(tribrachius),  or  only  two  (dibrachius)  and  a  very  rudimentary  third.  The 
lower  extremities  are  subject  to  the  same  variations  as  the  upper.  The  ex- 
ternal genitalia  and  anus  are  single.  The  alimentary  tube  is  double  as  far  as 
the  lower  end.  The  thoracic  viscera  are  partly  double.  Monsters  of  this 
type  may  live  for  years. 

Middle  Union. — In  the  case  of  middle  union  a  ventral  or  ventro-lateral 
attachment  extends  from  the  umbilicus  for  a  variable  distance  toward  the  head. 
In  most  cases  the  umbilicus  itself  is  single.  The  union  may  occur  in  the 
region  of  the  xiphoid  process — xiphopagus — or  it  may  involve  the  entire  region 
of  the  sternum — sternopagus  or  thoracopagus.  In  the  case  of  xiphopagus, 
a  bridge  joining  the  twins  extends  from  the  common  umbilicus  to  the 
xiphoid  processes.  The  latter  are  usually  united  across  the  bridge.  The 
thoracic  cavities  are  separate.  The  two  livers  may  be  connected  by  a  bridge  of 
hepatic  tissue,  in  which  case  the  two  peritoneal  cavities  are  in  communication, 
or  the  livers  may  remain  separate,  in  which  case  the  peritoneal  cavities  do  not 
communicate.  The  two  alimentary  tubes  may  or  may  not  communicate  in  the 
region  of  the  stomach.  Xiphopagi  may  live  for  many  years,  as  instanced  by 
the  "Siamese  Twins." 

In  the  case  of  sternopagus  the  union  extends  upward  from  the  common  um- 
bilicus, so  that  the  two  sterna  are  fused  into  a  single  bone.  There  is  a  com- 
mon thoracic  cavity,  separated  from  the  abdominal  cavity  by  a  single  diaphragm. 
One  or  two  hearts  may  be  present.  The  middle  portions  of  the  two  alimentary 
tubes  form  a  single  tract.  The  two  livers  are  fused  into  a  common  mass.  The 
genitalia  are  distinct  and  separate.  The  extremities  may  be  normal,  or  in  case 
of  a  ventro-lateral  union,  the  approximated  upper  extremities  may  be  fused. 
Such  monsters  are  usually  born  dead;  if  born  alive,  they  survive  but  a  short 
time  owing  to  defective  development  of  the  heart. 

As  other  varieties  of  thoracopagus  the  following  may  be  mentioned :  Thora- 
copagus parasiticus,  in  which  one  twin  is  much  arrested  in  development,  a  head 
and  heart  being  present,  and  attached  to  the  thoracic  region  of  the  stronger 
twin.  Gastrothoracopagus  dipygus  (dipygus  parasiticus),  in  which  extremities 
and  trunk  are  present  at  least  in  part  and  are  attached  to  the  lower  part  of  the 
thorax  or  to  the  epigastrium  of  the  other  twin.  The  head  is  not  present.  Such 
twins  may  live  for  years,  as  instanced  by  Laloo.  Cephalothoracopagus  diproso- 


598  TEXT-BOOK  OF  EMBRYOLOGY. 

fus}  in  which  the  attachment  may  extend  into  the  neck  and  head  region,  so 
that  there  is  a  union  from  the  head  to  the  umbilicus.  This  type  is  distinguished 
from  the  anterior  union  in  that  the  head  portions  of  the  twins  are  united 
laterally,  so  that  both  more  or  less  completely  developed  faces  are  turned 
toward  the  common  ventral  side,  while  the  bodies  have  their  ventral  sides 
directed  toward  each  other. 

Anterior  Union. — In  this  type  of  union  the  attachment  may  be  dorsal  and 
confined  to  the  head  (dorsal  anterior  union),  or  ventral  and  reaching  as  far  as 
the  umbilicus  (ventral  anterior  union). 

In  dorsal  union  the  heads  of  the  twins  are  joined  at  the  crowns,  so  that 
the  two  bodies  lie  in  a  straight  line,  or  form  an  angle  with  each  other.  Such 
a  monstrosity  is  known  as  craniopagus  (cephalopagus) .  The  attachment 
usually  involves  the  cranial  vault,  the  two  brains  remaining  separated  by 
their  membranes  within  a  common  cranial  cavity.  Such  monsters  are  rare 
and  survive  but  a  short  time.  A  very  rare  variety  of  craniopagus  is  the 
form  known  as  craniopagus  parasiticus,  in  which  one  twin  is  reduced  to  a 
rudimentary  structure  and  is  parasitic  upon  the  other.  In  all  the  above  cases 
the  term  autosite  is  applied  to  the  better  developed  twin. 

In  ventral  and  ventro-lateral  union  the  attachment  involves  the  head, 
neck  and  thorax — syncephalus,  cephalothoracopagus  janiceps.  The  twins  pass 
through  their  development  in  common,  each  individual  contributing  its 
quota  of  structure  to  the  composite  monster.  The  sternum  is  single,  the  oeso- 
phagus single,  the  larynx  and  trachea  double  or  single,  the  stomach  single,  the 
intestine  double.  The  two  hearts  may  be  united,  but  more  commonly  are 
separated,  one  being  situated  ventrally,  the  other  dorsally.  Two  faces  are 
formed,  one  belonging  to  each  embryo.  The  faces  may  be  alike  or  nearly  so 
(Janus  symmetros),  or  one  may  be  misplaced  or  unequally  developed  (Janus 
asymmetros),  which  often  results  in  cyclopia,  synotia,  or  obliteration  of  the 
opening  of  the  mouth. 

In  some  cases  the  greater  part  of  the  body  is  single  and  only  a  part  is  double 
(incomplete  duplicity).  The  malformation  may  affect  only  the  upper  end  or 
head  (superior  incomplete  duplicity),  or  only  the  lower  end  (inferior  incomplete 
duplicity).  In  the  former  case  the  skull  is  single,  with  possible  traces  of  a 
double  formation — diprosopus.  There  are  two  faces  with  varying  degrees  of 
fusion  between  them;  all  four  eyes  may  be  present,  or  the  two  approximated 
eyes  may  be  fused  or  they  may  be  wanting  (diprosopus  tetroph-,  trioph-, 
diophthalmus).  The  two  mouths  may  be  fused  (diprosopus  monostomus), 
and  with  a  greater  degree  of  fusion  between  the  faces  the  two  approximated 
ears  may  also  be  fused  or  be  entirely  lacking.  In  dicephalus  the  head  is 
double,  and  sometimes  the  upper  end  of  the  vertebral  column. 

Inferior  incomplete  duplicity  is  rare.     To  this  category  of  duplicate  monsters 


TERATOGENESIS.  599 

probably  belong  certain  cases  of  partial  duplicity  in  the  pelvic  region,  with 
sometimes  an  extra  set  of  genitalia.  Possibly  also  a  few  cases  of  a  third  lower 
extremity  would  come  under  this  head. 

Multiplicity. — Monochorionic  triplets  are  rare,  only  a  few  cases  being 
recorded.  Two  cases  of  monochorionic  quadruplets  are  on  record,  and 
one  case  of  quintuplets.  Incomplete  multiplicities  are  extremely  rare.  One 
case  of  incomplete  triplicity  has  been  described — tricephalus.  Two  verte- 
bral columns  were  present  in  this  monster,  bearing  one  and  two  heads  re- 
spectively. Two  thoracic  cavities,  each  enclosing  a  heart,  were  separated  by 
a  thin  septum.  The  abdominal  viscera  were  single.  The  lower  half  of  the 
body  and  the  lower  extremities  were  normal,  as  were  also  the  genital  organs, 
which  were  male. 

ORIGIN  OF  SYMMETRICAL  DUPLICITY. 

The  origin  of  duplicities  has  always  been  most  difficult  to  explain,  and 
the  many  solutions  suggested  have  been  replete  with  conjecture.  The  diffi- 
culty has  been  caused  by  the  lack  of  direct  observation  upon  formative  stages 
either  in  the  lower  or  higher  animals.  Within  recent  years,  however,  experi- 
mental work  upon  the  lower  forms  has  begun  to  throw  some  light  upon  this 
obscure  problem.  Among  the  theories  which  have  been  formulated  are  two 
that  stand  out  most  clearly — the  fusion  theory  (Marchand,  Ziegler)  and  the 
fission  theory  (Ahlfeld  and  others). 

According  to  the  fusion  theory,  there  are  present  two  originally  distinct 
anlagen  within  a  single  ovum.  These  two  anlagen  may  develop  separately  and 
independently  and  produce  twins.  They  may  come  in  contact  during  develop- 
ment and  fuse  to  a  greater  or  lesser  degree,  thus  producing  some  kind  of  dupli- 
cate monster.  If  fusion  does  occur  it  occurs  between  similar  parts  of  the  two 
anlagen;  in  other  words,  like  tissues  and  organs  fuse — liver  with  liver,  muscle 
with  muscle,  bone  with  bone,  and  so  on.  Such  unions,  however,  probably 
occur  only  in  very  early  stages  of  development,  for  when  tissues  are  once  formed, 
union  is  effected  with  much  greater  difficulty.  Consequently  fusions  between 
two  anlagen,  leading  to  double  monsters,  probably  take  place  at  a  very  early 
period  of  intrauterine  life. 

According  to  the  fission  theory,  duplicity  is  the  result  of  the  division  of  a 
single  anlage  in  the  earliest  stages  of  development,  before  the  formation  of  the 
primitive  streak.  The  cleavage  is  produced  by  mechanical  resistance  of  the 
zona  pellucida.  Since  the  greatest  mass  of  growing  material  is  in  the  head 
region,  the  resistance  is  greatest  there,  and  hence  it  is  argued  that  duplicities 
would  be  most  common  in  the  head  region,  which  accords  with  the  facts.  A 
modification  of  the  fission  theory  to  explain  duplicities  which  affect  a  relatively 
small  area  has  been  suggested.  Incomplete  anterior  duplicity,  for  example,  is 


600  TEXT-BOOK  OF  EMBRYOLOGY. 

not  the  result  of  fission  but  of  bifurcation  which  accompanies  the  development 
of  the  head  end  of  the  embryo  along  divergent  axes.  The  difference  between 
fission  and  bifurcation  is  that  the  former  is  the  passive  result  of  active 
mechanical  forces,  while  the  latter  is  a  part  of  active  formative  processes. 

Experiments  on  eggs  of  lower  animals  point  to  the  conclusion  that  each  of 
the  two  blastomeres  resulting  from  the  first  cleavage  contains  the  material 
necessary  to  produce  an  entire  body.  In  order  to  cause  a  blastomere  to  pro- 
duce a  whole  body,  however,  it  is  necessary  to  subject  it  to  unnatural  conditions. 
For  example,  if  one  of  the  two  primary  blastomeres  of  the  frog  is  killed  and  the 
other  left  to  grow  in  its  natural  position  it  will  produce  a  half-embryo;  but  if  the 
remaining  blastomere  is  inverted  it  will  produce  a  whole  embryo  (Morgan). 
On  the  other  hand,  in  view  of  certain  experiments  on  the  eggs  of  Amphioxus, 
it  has  been  asserted  that  duplicity  is  associated  with  double  gastrulation; 
when  these  eggs  were  shaken  during  the  first  cleavage,  some  developed  into 
double  gastrulae  (Wilson,  Hertwig).  For  a  further  discussion  of  these  causes, 
see  page  624. 

ASYMMETRICAL  DUPLICITY. 

In  this  type  of  malformation  the  two  anlagen  from  which  the  monster  is 
derived  are  primarily  dissimilar  and  unequal.  One  anlage  usually  remains  in 
a  rudimentary  condition,  bears  little  or  no  resemblance  to  a  foetus,  and 
becomes  a  parasite  upon  or  within  the  body  derived  from  the  other  anlage 
(parasite,  foetal  inclusion,  foetus  in  fcetu).  Sometimes,  however,  the  dependent 
embryo  may  develop  quite  complete  parts,  such  as  extremities,  but  always 
remains  attached  to  the  stronger  embryo,  from  which  it  derives  its  nourishment 
(implantation).  Parasitic  inclusions  and  implantations  may  be  attached  to 
the  autosite  in  the  region  of  the  head,  neck,  thorax,  abdomen,  etc. 

Parasitic  duplicities  in  the  head  region  may  take  the  form  of  masses  pro- 
truding from  the  orbital  region — prosopopagus  parasiticus  or  much  more  com- 
monly from  the  mouth — epignathus,  sphenopagus.  In  the  latter  case  the  tumor 
is  enveloped  by  skin  containing  hair  follicles  and  sweat  glands,  and  usually 
consists  of  cysts  and  intervening  embryonic  tissue.  It  sometimes  contains  teeth, 
cartilage,  bone,  fat  and  nerve  tissue,  even  traces  of  an  intestinal  canal  and 
of  liver  tissue.  One  epignathus  has  been  described  as  having  an  imperfect 
set  of  female  genitalia  which  lay  between  two  rudimentary  lower  extremities. 

Occasionally  irregular  tumors  are  found  in  the  region  of  the  pituitary  body 
(encranius),  which  contain  rudiments  of  various  tissues  and  organs.  In  such 
cases  the  parasitic  anlage  has  possibly  been  included  during  the  imagination 
which  forms  the  oral  part  of  the  pituitary  body.  Tumors  consisting  of  various 
tissues,  such  as  lymphatic,  adipose,  muscle,  etc.,  are  also  found  in  the  brain 


TERATOGENESIS.  601 

ventricles.  They  possibly  represent  parasitic  anlagen  which  have  become  en- 
closed within  the  brain  vesicles  as  the  neural  groove  closed  in  dorsally. 

Certain  foetal  inclusions  attached  to  the  region  formed  by  the  branchial 
arches  are  spoken  of  as  cervical  parasites.  These  are  usually  cystic  tu- 
mors, covered  with  skin  and  containing  teeth,  bone  and  parts  of  a  head  and 
extremities. 

Closely  associated  with  the  cervical  parasites  is  a  group  of  tumors  found 
within  the  anterior  mediastinum  in  the  region  of  the  thymus  gland,  and  known 
as  thoracic  parasites.  It  must  be  borne  in  mind,  however,  that  some  of  the 
tumors  found  in  the  cervical  and  thoracic  regions  are  not  true  parasitic  in- 
clusions, but  are  dermoid  cysts  (resembling  the  parasites)  derived  from  the 
ectoderm.  True  parasitism  implies  origin  from  all  three  germ  layers.  From 
a  structural  standpoint  it  is  sometimes  very  difficult,  even  impossible,  to  distin- 
guish between  true  parasitic  inclusions  and  dermoid  cysts  that  are  derived  from 
ectoderm. 

Very  rarely  in  the  human  subject  some  parasitic  structure  is  attached  to  the 
back.  One  case  of  a  supernumerary  penis  in  the  lumbar  region  has  been  de- 
scribed; another  case  is  on  record  of  an  almost  complete  set  of  female  genitalia 
on  the  back  of  a  male.  Such  malformations  can  be  explained  only  by  assum- 
ing the  partial  development  of  another  embryonic  anlage. 

Sacral  parasites  are  the  most  frequent  of  the  true  parastic  growths.  These 
are  cystic  tumors  which  are  attached  to  and  hang  from  the  sacrum  or  the 
coccyx.  The  tumors  are  covered  with  skin  which  blends  with  the  skin  of  the 
autosite.  In  the  existence  of  such  elements  as  fat,  bone,  muscle,  and  nerves, 
and  the  rudiments  of  intestines  and  extremities  is  found  the  evidence  of  their 
fcetal  origin. 

Foetal  inclusions  in  the  abdominal  region  are  not  frequent.  One  very  rare 
intraparietal  (or  subcutaneous)  inclusion,  in  a  child  two  and  one-half  years 
old,  proved  to  be  a  cystic  tumor  which  contained  a  fairly  well  formed  foetus 
with  defective  head  and  extremities.  Engastric  (intraabdominal)  parasites 
are  usually  found  in  the  region  of  the  lesser  peritoneal  sac,  at  the  root  of  the 
transverse  mesocolon.  These  tumors  are  usually  enclosed  within  a  sac  of 
mesenteric  or  peritoneal  tissue.  There  may  be  well  marked  fcetal  structures, 
such  as  head,  trunk,  extremities,  etc.,  or  only  traces  of  rudimentary  organs. 
The  presence  of  an  intraabdominal  parasite  does  not  necessarily  cause  the 
death  of  the  autosite  immediately  after  birth;  for  one  case  in  particular  is  on 
record  in  which  the  autosite  (a  boy)  lived  to  be  fifteen  -ears  old  with  a  parasite 
that  was  capable  of  independent  movement. 

Parasitic  Structures  in  the  Sexual  Glands. — The  type  of  tumor  referred  to 
here  forms  a  group  that  is  of  especial  interest  owing  to  their  relative  frequency 
of  occurrence  and  to  their  peculiar  mode  of  production.  In  connection  with 


602  TEXT-BOOK  OF  EMBRYOLOGY. 

the  ovary  dermoid  cysts  and  other  solid  masses  occur.  The  cysts  consist  of  a 
sac  enclosing  hair  and  adipose  tissue;  not  infrequently  teeth  are  also  present,  as 
well  as  sebaceous  and  sweat  glands.  Sometimes  there  are  also  bone,  cartilage, 
muscle,  and  nerve  tissue  and  traces  of  the  digestive  and  respiratory  systems  and 
of  thyreoid  gland;  more  rarely  traces  of  mammary  glands,  finger  nails  and 
retinal  pigment  are  present.  In  the  rarer  solid  tumors  that  develop  in  rela- 
tion to  the  ovary  all  three  germ  layers  are  represented,  but  their  derivatives 
are  more  rudimentary  and  not  so  regularly  arranged  as  in  the  cysts. 

Parasitic  growths  in  the  testis  are  much  less  frequent  than  in  the  ovary. 
The  cysts  are  rarer  than  the  solid  masses.  These  are  probably  homologous 
with  the  parasites  of  the  ovary. 

ORIGIN  OF  ASYMMETRICAL  (PARASITIC)  DUPLICITY. 

Parasitic  duplicity  implies  primary  inequality  of  the  embryonic  anlagen;  in 
other  words,  the  anlage  of  the  parasite  is  inferior,  so  to  speak,  to  the  anlage  of 
the  host.  During  development  the  inequality  or  asymmetry  persists  or  be- 
comes more  conspicuous  until  the  parasite  is  more  or  less  enclosed  within  the 
autosite.  As  the  autosite  develops  in  a  manner  at  least  simulating  the  normal, 
the  parasite  remains  in  a  more  or  less  rudimentary  condition,  with  perhaps  only 
a  few  tissues  which  show  any  differentiation.  In  some  cases  the  parasite 
becomes  enclosed  partially  or  completely  within  the  autosite  (epignathus) ,  in 
other  cases  the  parasitic  growth  apparently  occurs  primarily  within  the  autosite 
(ovarian  cysts). 

The  manner  in  which  the  rudimentary  anlage  becomes  surrounded  by  the 
more  nearly  perfect  anlage  is,  of  course,  not  known  through  direct  observation. 
But  it  seems  reasonable  to  assume  that  such  enveloping  occurs  in  connection 
with  or  as  a  part  of  the  normal  processes  of  folding  by  which  the  external  form 
of  the  body  is  established.  This  folding  occurs  at  the  cephalic  and  caudal  poles 
of  the  embryonic  disk  and  also  along  its  entire  length.  In  addition  there  is 
also  the  folding  in  of  the  neural  groove  along  the  dorsum  of  the  embryo,  and 
the  invagination  of  the  branchial  grooves.  One  can  readily  imagine  the  para- 
sitic anlage  as  attached  to  some  one  of  the  areas  that  are  folded  in,  so  that 
it  is  carried  wholly  or  partially  into  the  interior  of  the  stronger  embryonic 
anlage  and  becomes  surrounded  by  the  tissues  of  the  autosite  to  produce  a 
true  foetal  inclusion. 

There  seems  to  be  little  doubt  as  to  the  existence  of  a  second,  more  or  less 
rudimentary  anlage  which  becomes  the  parasite;  in  other  words,  there  is  almost 
certainly  a  duplicity  to  begin  with,  although  it  may  be  an  asymmetrical  one. 
It  is  also  plausible  to  assume  that  for  a  time  the  weaker  anlage  develops  in- 
dependently of  the  stronger,  but  that  later  it  is  dependent  upon  the  stronger 


TERATOGENESIS.  603 

for  its  nutrition.  The  problem,  however,  is  to  explain  the  origin  of  the  rudi- 
mentary anlage  which  produces  the  parasite.  In  view  of  the  facts  concerning  the 
early  stages  of  development — the  facts  concerning  maturation,  fertilization  and 
segmentation  of  the  ovum,  and  the  formation  of  the  germ  layers — there  are  two 
possible  and  plausible  modes  of  origin  of  the  rudimentary  anlage.  (i)  The 
anlage  of  the  parasite  may  be  the  result  of  the  imperfect  development  of  a 
fertilized  polar  body.  (2)  The  anlage  of  the  parasite  may  be  a  special  or  an 
isolated  group  of  segmentation  cells. 

1.  It  is  generally  agreed  that  the  polar  bodies  are  abortive  or  rudimentary 
ova  extruded  during  the  processes  of  maturation  of  the  female  sex  cell;  and  that 
these  rudimentary  ova  probably  contain  the  same  morphological  constituents 
as  the  mature  ovum  itself.     It  is  also  known  that  in  a  few  of  the  lower  forms 
the  polar  bodies  arc  capable  of  being  fertilized  and  undergoing  a  considerable 
degree  of  development,  and  that  in  some  of  the  higher  forms  (rabbit,  dog)  the 
spermatozoa  may  exist  for  some  time  inside  the  zona  pellucida  in  the  vicinity 
of  the  polar  bodies.     In  view  of  these  facts  it  does  not  seem  impossible  that  in 
a  few  exceptional  cases  in  Mammals  the  polar  bodies  may  become  fertilized 
and  produce  rudimentary  anlagen  capable  of  giving  rise  to  parasites.     Such 
an  anlage  would  naturally  lie  in  close  proximity  to  the  larger  normal  anlage 
and    might   readily  become  attached  to  or  finally  enclosed  within  it.     As  a 
more  remote  possibility,  the  polar  body  might  become  enclosed  between  the 
blastomeres  and  thus  finally  produce  the  parasitic  anlage  within  the  meso- 
dermal  tissue  where  it  might  become  an  inclusion  in  some  internal  organ, 
such  as  the  genital  gland.     A  polar  body  has  been  found  between  the  blasto- 
meres (rabbit).     (Bischoff,  Assheton,  Bonnet.) 

2.  The  view  that  the  parasite  may  arise  as  the  result  of  the  development  of  a 
special  or  an  isolated  group  of  segmentation  cells  has  more  advocates  than  the 
view  given  in  the  preceding  paragraph.     One  of  the  most  interesting  phases  of 
this  theory  is  the  view  that  tumors  of  the  sexual  glands,  as  well  as  those  of  other 
regions,  are  the  products  of  development  of  the  germ  cells  as  distinguished  from 
the  somatic  cells.     In  the  skate  it  has  been  demonstrated  that  certain  cells  are 
set  apart  at  a  very  early  period  of  development  (during  segmentation),  which 
are  destined  to  give  rise  to  the  sex  cells  of  the  embryo,  and  which  take  no 
part  in  its  general  development.     Normally  these  special  cells  pursue  a  course 
of  development  and  differentiation  which  leads  to  the  formation  of  the  mature 
sexual  elements  (ova  or  spermatozoa)  of  the  individual,  but  do  not  participate 
in  its  general  development.     From  this  one  may  conclude  that  the  primitive 
germ  cell,  the  one  set  apart  for  the  production  of  the  mature  sex  cells,  is,  so 
to  speak,  a  sister  to  the  embryo  and  is  not  a  derivative  of  the  embryo.     It 
seems  not  impossible  that  some  aberrant  members  of  this  group  of  germ  cells, 
without  undergoing  the  changes  incident  to  maturation,  might  pursue  a  course 


604  TEXT-BOOK  OF  EMBRYOLOGY. 

of  development  of  their  own  accord  and  give  rise  to  a  rudimentary  twin — the 
foetal  inclusion  or  parasite.  In  this  case  one  must  regard  the  germ  cells  as  pos- 
sessing an  inherent  potentiality  which  may  institute  formative  processes;  but  the 
actual  cause  of  the  spontaneous  development  is  unexplained.  (Born,  Wilson, 
Morgan,  Driesch,  Schultze). 

Another  possible  source  of  parasitic  growths  is  suggested  by  experiments  in 
which  some  of  the  cells  during  segmentation  have  been  separated  from  the 
general  mass.  The  artificially  segregated  cells  may  develop  into  perfect  em- 
bryos smaller  than  the  normal,  or  into  partial  embryos.  Further  experiments 
along  the  same  line  on  the  frog  justify  the  assumption  that  the  segregated  cells 
or  masses  may  become  enclosed  within  the  developing  larger  embryo  and  there 
undergo  further  growth  and  differentiation  and  give  rise  to  inclusions  or 
parasites.  (Roux.) 

As  a  matter  of  fact  there  seems  to  be  no  good  reason  for  considering  any  one 
of  the  above  views  as  expressing  the  only  possibility  as  to  the  source  of  unequal 
duplicities  or  parasitic  growths.  There  is  nothing  to  show  that  all  three 
methods  may  not  contribute  to  the  various  kinds  of  duplicities  including 
certain  teratomata  of  the  sexual  glands. 

MALFORMATIONS  INVOLVING  ONE  INDIVIDUAL. 

Description,  Origin. 

While  the  more  limited  malformations  and  anomalies  affecting  individual 
organs  are  discussed  in  the  chapters  dealing  with  those  organs,  it  seems  best 
to  consider  here  some  of  the  gross  malformations  in  a  single  individual, 
especially  those  which  affect  the  external  form  of  the  body. 

DEFECTS  IN  THE  REGION  OF  THE  NEURAL  TUBE. 

The  term  cranioschisis  has  been  given  to  a  group  of  malformations,  or 
defects,  in  the  roof  of  the  skull  and  in  the  brain.  Depending  upon  the  degree 
of  defect,  the  group  is  divided  into  two  classes — acrania  and  hemicrania — 
which  include  conditions  from  a  complete  absence  of  the  roof  of  the  skull  to 
partial  arrest  of  development.  Associated  with  these  conditions  are  varied 
defects  and  malpositions  of  parts  or  of  the  whole  of  the  brain. 

In  extensive  acrania  the  entire  roof  of  the  skull  is  lacking,  and  the  brain 
and  its  membranes  are  reduced  to  small  masses  of  tissue  lying  upon  the  floor 
of  the  skull.  The  defect  may  also  extend  to  the  cervical  vertebrae — crania- 
rachischisis.  These  vertebras  remain  open  dorsally  and  are  bent  inward 
(lordosis) .  The  ears  are  set  upon  the  shoulders  and  the  neck  seems  to  be 
lacking. 


TERATOGENESIS.  605 

Sometimes  the  rudimentary  brain  shows  traces  of  structures  which  the 
normal  brain  possesses,  and  is  raised  above  the  level  of  the  defective  skull  like 
a  turban — acrania  with  exericephaly.  With  acrania  are  usually  associated 
facial  clefts,  defects  in  the  eyes,  etc. 

The  malformation  known  as  hemicrania  is  limited  to  a  part  of  the  skull, 
usually  the  posterior  part.  The  brain  mass  often  protrudes  through  an  opening 
in  the  cranial  vault  and  forms  a  mass  on  the  back  of  the  head  or  hanging  down 
upon  the  neck — hemicrania  with  exencephaly. 

In  the  various  forms  of  cephalocele  or  cerebral  hernia  the  roof  of  the  skull  is 
more  nearly  complete  and  the  protrusion  of  the  cranial  contents  is  limited 
to  circumscribed  areas.  The  protruding  mass  may  consist  of  brain  substance 
only — encephalocele,  or  of  the  membranes  only — mcningocele,  or  of  both — 
meningoencephalocele.  Sometimes  the  brain  ventricles  are  distended  by  the 
accumulation  of  fluid — hydr encephalocele,  or  a  sac  formed  by  the  membranes 
may  be  distended  by  fluid — hydromeningocele. 

A  condition  known  as  hydrencephaly  is  sometimes  met  with.  Fluid  ac- 
cumulates in  the  brain  cavities  after  the  skull  is  formed,  causing  a  general 
enlargement  of  both  brain  and  skull,  without  hernia  (congenital  hydrocephaly) . 

A  combination  of  hydrencephaly  and  cephalocele  may  also  occur.  The 
cervical  vertebrae  adjoining  the  skull  are  cleft  dorsally  and  the  protruding  mass 
lies  in  the  cleft — iniencephaly. 

Hydromicrencephaly  means  an  accumulation  of  fluid  with  a  rudimentary 
brain  and  a  correspondingly  small  skull. 

Porencephaly  is  a  lower  grade  of  hydromicrencephaly,  in  which  fluid  ac- 
cumulates in  the  third  and  lateral  ventricles  and  affects  the  adjacent  frontal 
and  parietal  lobes.  If  the  individual  lives  with  this  malformation,  the  intellect 
is  impaired  and  the  extremities  contract  and  atrophy. 

Microcephaly  and  micrencephaly  go  together  as  abnormal  smallness  of  the 
skull  and  brain.  The  brain,  aside  from  the  diminutive  size,  may  not  be  de- 
formed. These  conditions,  in  which  the  body  is  of  the  usual  size,  should  not 
be  confused  with  those  found  in  dwarfs  in  whom  the  body  also  is  small 
(nanocephaly). 

In  the  region  of  the  spinal  cord  there  is  a  group  of  malformations  consisting 
of  varying  degrees  of  clefts  in  the  vertebral  canal.  The  clefts  may  remain  open 
— rachischisis — or  they  may  be  covered  by  a  sac-like  prominence — spina  bifida 
(spina  bifida  cystica,  rachischisis  cystica).  Both  forms  of  cleft  may  occur  in 
any  region  of  the  vertebral  column  and  may  be  limited,  or  involve  the  entire 
column. 

The  malformation  known  as  rachischisis  appears  as  a  widely  open  groove 
bounded  laterally  by  rudimentary  laminae  of  the  vertebrae.  The  deformity  may 
include  the  entire  vertebral  column — holorachischisis,  or  it  may  be  confined  to 


606  TEXT-BOOK  OF  EMBRYOLOGY. 

a  small  part — merorachischisis,  and  is  usually  accompanied  by  curvature  of  the 
spine.  Sometimes  the  deformity  of  the  vertebral  column  is  continuous  with 
cranioschisis — craniorachischisis.  The  more  or  less  rudimentary  spinal  cord 
lies  along  the  bottom  of  the  cleft.  When  the  rachischisis  is  total  the  spinal 
cord  is  practically  wanting — amyelus. 

Spina  bifida  is  marked  by  the  presence  of  a  cyst  which  protrudes  through  a 
cleft  in  the  vertebral  column;  externally  it  presents  the  appearance  of  a  sac- 
like  structure  of  variable  size.  Three  different  types  of  spina  bifida  may  be 
recognized,  depending  upon  the  structures  involved.  If  the  cord  and  its  mem- 
branes are  included  in  the  cyst  it  is  known  as  myelomeningocele;  if  only 
the  membranes,  as  spinal  meningocele;  if  the  cord  itself  is  dilated,  as  myelo- 
cystocele. 

Myelomeningocele  is  the  most  common  form  of  spina  bifida  and  usually 
occurs  in  the  lumbo-sacral  region,  rarely  in  the  cervical  or  thoracic  region. 
Its  appearance  is  that  of  a  rounded  tumor  in  the  medial  line,  and,  if  the  child 
lives,  the  tumor  increases  in  size  and  may  become  as  large  as  a  child's  head. 
The  spinal  cord  is  bent  dorsally  and  attached  to  the  sac.  The  pia  mater  and 
arachnoid  surround  the  cord,  while  the  dura  is  incomplete.  The  spinous 
processes  and  the  adjacent  parts  of  the  arches  of  the  vertebrae  are  absent. 
From  one  to  several  vertebrae  may  be  affected. 

In  spinal  meningocele  the  spinal  membranes  bulge  out  to  form  a  sac  filled 
with  fluid.  The  vertebrae  are  not  necessarily  defective,  for  the  sac  may  pro- 
trude between  the  arches  or  through  the  intervertebral  foramina;  it  more 
often  protrudes  laterally  than  dorsally.  The  presence  of  meningocele  is 
not  at  all  incompatible  with  life,  but  the  sac  usually  enlarges  to  a  good-sized 
tumor. 

In  myelocystocele  (syringomyelocele)  the  central  canal  of  the  spinal  cord  is 
dilated  locally,  with  the  result  that  a  portion  of  the  cord  with  the  pia  and 
arachnoid  becomes  a  cystic  tumor.  It  may  occur  in  any  region,  and  is  fre- 
quently associated  with  asymmetrical  defects  of  the  vertebral  column. 

Spina  bifida  occulta,  a  condition  in  which  neither  cleft  nor  tumor  is  visible 
externally,  is  usually  found  in  the  lumbo-sacral  region.  The  position  of  the 
defect  is  indicated  by  a  small  depressed  cicatrix  or  by  a  small  tuft  of  hair. 
The  spinal  cord  is  elongated  and  extends  into  the  sacral  canal.  The  spinal 
canal  is  sometimes  dilated  and  the  cauda  equina  affected,  in  consequence  of 
which  there  are  sensory  and  motor  disturbances  in  the  lower  extremities. 
Paralytic  club-foot  and  derangement  of  the  bladder  functions  may  result 
from  such  a  deformity  of  the  cord. 

Diastematomyelia,  or  doubling  of  the  spinal  cord,  sometimes  accompanies 
rachischisis.  The  cord  in  such  cases  is  represented  by  two  atrophic  bands. 


TERATOGENESIS.  607 

ORIGIN  OF  MALFORMATIONS  IN  THE  REGION  OF  THE  NEURAL  TUBE. 

Normally  the  neural  tube  is  formed  from  a  band  of  ectoderm  extending 
along  the  dorsum  of  the  embryonic  disk.  The  ectodermal  band  becomes 
thickened,  a  groove  appears  along  the  middle  line  and  the  margins  are  raised 
above  the  surface  of  the  embryo,  forming  the  neural  groove.  The  margins  of 
the  band  continue  to  push  upward  and  finally  meet  and  fuse  with  each  other 
throughout  their  entire  length  in  the  middorsal  line.  The  surface  ectoderm 
then  breaks  away  from  the  line  of  fusion  and  forms  a  continuous  layer  upon  the 
dorsum  of  the  embryo,  thus  leaving  the  neural  groove,  now  the  neural  tube, 
extending  the  entire  length  of  the  embryo  immediately  beneath  the  ectoderm. 

The  formation  of  the  neural  tube  is  a  fundamental  process,  occurring 
at  an  early  period.  It  is  obvious  that  any  interference  with  its  development 
will  be  followed  by  serious  defects  in  the  nervous  system  and  the  structures 
that  immediately  surround  it.  A  most  natural  result  of  such  interference  would 
be  the  failure  of  the  two  margins  of  the  neural  groove  to  unite,  and  it  is  not 
improbable  that  the  various  forms  of  cranioschisis  are  the  results  of  imperfect 
or  complete  lack  of  closure  of  the  cephalic  end  of  the  neural  groove.  Such 
failure  of  the  neural  groove  to  close  would  leave  the  dorsum  of  the  head  region 
open,  so  that  not  only  the  brain  but  also  the  cranial  vault  would  be  affected. 
If  the  failure  to  close  is  complete,  a  high  degree  of  acrania  would  result.  In 
case  of  partial  closure  some  form  of  hemicrania  might  follow. 

Rachischisis,  with  partial  or  total  absence  of  the  spinal  cord,  may  also  be 
attributed  to  defective  closure  of  the  neural  tube,  total  rachischisis  being  due  to 
complete  lack  of  closure,  partial  rachischisis  to  partial  lack  of  closure. 

The  origin  of  spina  bifida  has  been  a  much  discussed  question.  The  earlier 
view  that  the  deformity  was  due  to  accumulation  of  fluid  within  the  spinal  canal 
and  rupture  of  the  distended  sac  is  now  usually  considered  untenable.  At  the 
present  time  it  is  generally  agreed  that  spina  bifida  is  closely  related  to  defective 
closure  of  the  neural  tube,  although  the  exact  nature  of  this  relation  is  not 
known. 

According  to  one  investigator  the  defective  fusion  of  the  margins  of  the 
neural  groove  is  due  to  deficient  growth  of  the  blastoderm  (von  Reckling- 
hausen).  Another  view  is  that  the  separation  between  the  neural  tube  and 
the  adjacent  ectoderm  is  incomplete  (Torneux).  Still  another  investigator 
considers  the  defective  development  due  to  some  primary  defect  in  the  germ 
(Ziegler).  Experimental  studies  on  the  frog's  egg  suggest  to  another  observer 
that  spina  bifida  is  caused  by  defective  closure  of  the  blastopore  (Hertwig). 
Recently  it  has  become  possible  to  produce  spina  bifida  at  will  in  some  of  the 
lower  Vertebrates  (frog,  Axolotl)  by  treating  the  developing  eggs  with  a  solution 
of  sodium  chlorid  (Hertwig).  At  the  same  time  other  defects  in  the  nervous 


608  TEXT-BOOK  OF  EMBRYOLOGY. 

system  (anencephaly)  are  produced.     In  these  experiments  the  malformations 
follow  retarded  closure  or  lack  of  closure  of  the  neural  tube. 

DEFECTS  IN  THE  REGION  OF  THE  FACE  AND  NECK,  AND  THEIR  ORIGIN. 

Associated  with  malformations  of  the  brain  there  is  a  group  of  defects  which 
involve  the  eyes  and  nose,  and  to  which  the  term  cydocephaly  has  been  applied. 
The  cerebral  hemispheres  are  derivatives  of  the  fore-brain.  Sometimes  they 
fail  to  develop  properly  and  are  represented  by  a  single  mass  occupying  a 
considerable  portion  of  the  cranial  cavity.  The  eyes  primarily  represent 
lateral,  symmetrical  outgrowths  from  the  fore-brain  vesicle.  If  the  cerebral 
hemispheres  fail  to  develop,  the  development  of  the  eyes  is  profoundly  influ- 
enced. Instead  of  being  widely  separated  there  may  be  any  degree  of  mal- 
formation from  a  mere  narrowing  of  the  distance  between  them  to  a  complete 
fusion  into  a  single  organ  within  a  single  medial  orbit — synophthalmia  or  cyclo- 
pia.  Within  this  orbit  the  eye  may  possess  double  or  partially  blended  cor- 
neae,  pupils,  lenses,  and  optic  nerves,  or  it  may  have  single  structures. 

Since  the  fronto-nasal  process,  which  plays  an  important  part  in  the  forma- 
tion of  the  nose,  depends  for  its  normal  shape  upon  the  development  of  the  fore- 
brain  region,  various  degrees  of  malformation  of  the  nose  almost  invariably 
accompany  cyclopia.  In  a  typical  cyclops  the  nose  is  reduced  to  a  fleshy  mass 
protruding  from  the  frontal  region. 

It  is  not  unusual  to  find  clefts  of  the  upper  lip  (hare  lip)  and  of  the  palate 
(cleft  palate)  associated  with  cyclopia;  for  the  normal  union  of  the  fronto- 
nasal  and  maxillary  processes  depends  upon  the  development  of  the  fore-brain 
region.  The  branchial  arches  likewise  may  be  affected  with  resulting  mal- 
formations of  the  mouth  and  external  ear.  The  two  ears  may  be  united  across 
the  ventro-medial  line — synotus  or  cydotus,  and  the  mouth  slit  may  be  absent— 
cydostomus. 

The  eye  may  also  be  the  seat  of  local  defects.  It  may  remain  abnormally 
small — micr ophthalmia,  or  incompletely  developed,  or  may  be  entirely  lacking 
— anophthalmia.  The  eyelids  may  enclose  an  abnormally  narrow  fissure — 
ankyloblepharon,  or  the  fissure  may  be  wanting — cryptophthalmia,  or  the  lids 
may  be  adherent  to  the  eyeball — symblepharon.  Sometimes  there  is  a  cutaneous 
fold  which  partly  fills  the  inner  canthus  like  the  nictitating  membrane  in  lower 
forms — epicanthus. 

Malformations  of  the  face  are  not  uncommon,  all  such  congenital  defects 
being  due  to  incomplete  fusion  of  the  processes  which  form  the  jaws  and 
greater  part  of  the  face  (see  page  148).  In  extreme  cases  there  is  an  early 
and  complete  arrest  of  development  of  all  the  parts  which  normally  form  the 
face — aprosopus.  Arrested  development  of  the  first  pair  of  branchial  arches 


TERATOGENESIS.  609 

results  in  abnormally  small  lower  jaws — micrognaihy,  or  in  almost  complete 
absence  of  the  lower  jaws — agnathus;  in  the  latter  case  the  ears  are  brought 
together  in  the  ventro-medial  line — synotus.  Rarely  the  mandible  is  partly 
duplicated,  due  to  the  development  of  a  secondary  mandibular  process — 
dignathus. 

Clefts  in  the  upper  lip,  maxilla  and  palate  follow  the  lines  of  primary  union 
of  the  processes  which  form  these  structures  (consult  Figs.  136  and  137).  The 
cleft  may  affect  the  lip  alone,  may  be  single  or  double,  but  is  always  lateral — 
hare  lip  (cheiloschisis).  It  may  affect  the  lip  and  maxilla  (cheilognathoschisis) , 
or  the  lip,  maxilla  and  palate  (hare  lip  and  cleft  palate,  cheilognathouranos- 
chisis).  (For  a  further  discussion  of  hare  lip  and  cleft  palate,  see  p.  212). 

Occasionally  there  is  an  entire  lack  of  union  between  the  naso-frontal  process 
and  the  maxillary  process.  The  result  is  an  oblique  cleft  which  extends  up- 
ward from  the  mouth — oblique  facial  cleft  (cheilognathoprosoposchisis) .  The 
processes  which  form  the  boundaries  of  the  mouth  slit  (maxillary  and  mandib- 
ular processes)  sometimes  fail  to  fuse  to  the  normal  extent,  thus  giving  rise  to 
macrostomus;  or  the  fusion  may  proceed  beyond  the  normal  limit,  giving  rise  to 
microstomus;  rarely  complete  fusion  of  the  processes  on  one  side  with  each  other 
and  with  their  fellows  of  the  opposite  side  results  in  closure  of  the  mouth  slit — 
astomus  or  atresia  oris.  Clefts  in  the  lower  lip,  due  to  imperfect  union  of  the 
two  mandibular  processes  in  the  medial  line,  are  rare. 

The  branchial  arches  (apart  from  the  first  which  has  already  been  con- 
sidered) and  the  branchial  grooves  are  also  subject  to  defective  developmental 
processes.  Malformations  of  the  ear,  with  closure  of  the  external  auditory 
meatus,  due  to  abnormal  development  of  the  first  groove  and  surrounding  parts, 
are  sometimes  met  with  either  alone  or  in  connection  with  other  facial  defects. 
Cervical  fistula  are  the  results  of  imperfect  closure  of  some  of  the  grooves  along 
with  rupture  of  the  membranes  that  separate  the  bottoms  of  the  external 
grooves  from  the  bottoms  of  the  internal  grooves  or  pharyngeal  pouches.  The 
fistula  may  be  complete,  that  is,  there  may  be  a  communication  between  the 
pharyngeal  cavity  and  the  exterior;  or  it  may  be  incomplete,  opening  either 
into  the  pharynx,  or  on  the  surface  of  the  body.  The  internal  opening  of  a 
cervical  fistula  is  usually  in  the  lower  part  of  the  pharynx  or  in  the  posterior 
palatine  arch  near  the  tonsil.  The  external  opening  varies  in  position.  It  is 
usually  situated  near  the  sterno-clavicular  articulation,  or  at  the  inner  or 
outer  edge  of  the  sterno-mastoid  muscle.  The  majority  of  cervical  fistulae  are 
probably  derived  from  the  second  branchial  groove.  They  all  have  the  form  of 
narrow  canals  lined  with  mucous  membrane.  Medial  cervical  fistulae,  the  ex- 
ternal openings  of  which  are  situated  in  the  medial  line,  are  rare. 

It  sometimes  happens  that  during  the  closure  of  the  branchial  grooves  por- 
tions of  the  walls  of  the  grooves  becomes  enclosed  within  the  walls  of  the 


610  TEXT-BOOK  OF  EMBRYOLOGY. 

pharynx,  that  is,  within  the  sides  of  the  neck.  This  abnormal  process  results  in 
various  forms  of  cysts  and  tumors.  The  most  common  are  simple  retention 
cysts,  known  as  branchial  or  branchio  genetic  cysts,  which  vary  from  small 
insignificant  structures  to  large  tumors.  If  derived  from  the  external  branchial 
furrows,  they  are  dermoid  in  character,  lined  with  ectodermal  derivatives,  and 
contain  sebaceous  material.  If  derived  from  the  internal  furrows,  they  con- 
tain mucous  fluid,  the  lining  epithelium  is  likely  to  be  columnar  and  is  claimed 
by  some  to  be  ciliated. 

DEFECTS  IN  THE  THORACIC  AND  ABDOMINAL  REGIONS,  AND  THEIR  ORIGIN. 

As  described  elsewhere  (see  page  316),  the  digestive  tube  (primitive  gut)  and 
ventral  body  wall  are  formed  primarily  by  a  bending  ventrally  and  fusing  of  the 
originally  flat  germ  layers.  The  splanchnopleure  on  each  side  first  bends 
ventrally  and  fuses  with  its  fellow  of  the  opposite  side  in  the  medial  line  to  form 
the  gut,  and  soon  afterward  the  somatopleure  likewise  fuses  in  the  ventro- 
medial  line  to  form  the  body  wall.  Naturally  a  defective  fusion  of  the  two 
sides  of  the  somatopleure  would  result  in  a  more  or  less  extensive  medial  cleft. 
The  cleft  may  be  limited  to  a  small  portion  of  the  abdomen  or  thorax,  or  may 
extend  from  the  neck  to  the  pelvis. 

When  the  cleft  is  very  extensive  and  involves  the  thoracic  and  abdominal 
walls,  the  condition  is  known  as  thoracogastroschisis.  In  this  case  most  of  the 
viscera  protrude  through  the  cleft  (ectopia  viscerum)  and  are  covered  merely 
by  peritoneum.  Spinal  curvature  of  a  low  or  high  degree  is  usually  associated 
with  the  eventration. 

The  cleft  may  involve  the  entire  abdominal  wall — gastroschisis  completa— 
and  the  abdominal  viscera  may  protrude  through  it.  In  a  somewhat  lesser 
degree  of  fission,  parts  of  the  abdominal  viscera,  covered  with  peritoneum, 
may  protrude  and  form  what  is  known  as  omphalocele.  Not  uncommonly 
portions  of  the  intestine  and  omentum  protrude  through  an  abnormally  large 
umbilical  ring — umbilical  hernia.  The  region  below  the  umbilicus  is  not  in- 
frequently the  seat  of  fissures  in  the  abdominal  wall,  through  which  the  bladder 
may  protrude  (ectopia  vesicas) .  Fissures  in  the  thoracic  wall  vary  in  extent. 
When  the  defect  is  extensive  the  heart  and  pericardium  protrude  through  the 
opening  (ectopia  cordis). 

MALFORMATIONS  OF  THE  EXTREMITIES. 

Any  degree  of  deficiency  may  exist,  from  total  absence  of  extremities  to 
the  lack  of  a  single  finger.  The  malformations,  however,  are  not  confined  to 
total  or  partial  lack  of  members,  for  supernumerary  fingers  and  toes  are  some- 
times present.  The  following  is  the  classification  given  by  Piersol: 


TERATOGENESIS.  611 

1.  One  or  More  Extremities  Wanting. — (a)  Amelus.     Both  upper  and  lower 
extremities  are  practically  absent,     (b)  Abrachius,  A  pus.     Either  the  upper  or 
lower  extremities  are  wanting,  the  other  pair  often  being  well  formed,     (c) 
Monobrachius,  Monopus.     One  upper  or  one  lower  extremity  is  absent,  the 
others  being  fully  developed. 

2.  One  or  More  Extremities  Defective. — (a)  Peromelus.     All  the  extremities 
are  imperfect.     A  striking  variety  of  this  is  the  suppression  of  the  proximal 
segments  of  the  extremities,  the  hands  and  feet  being  fairly  well  formed  (phoco- 
melus).     (b)  Perobrachius,  Per  opus.     The  former  signifies  defective  develop- 
ment of  the  upper,  the  latter  of  the  lower  extremities. 

3.  One  or  More  Extremities  Abnormally  Small  but  well  Formed. — (a)  Micro- 
melus.    All  the  extremities  are  diminutive,  but  without  any  other  malformation, 
(b)   Microbrachius,  Micropus.     One  or  both  upper  extremities  may  be  small,  or 
one  or  both  lower. 

4.  Bones  Defective  or  Absent. — Such  malformations  are  rare. 

5.  Loii'er  Extremities  Fused. — (a)  Sympus  (symelus  siren).     The  lower  ex- 
tremities are  fused  more  or  less  completely,  and  the  lower  end  of  the  trunk  is 
abnormal.     The  feet  may  be  imperfect  and  double  (sympus  dipus) ,  or  a  single 
foot  may  be  present  (sympus  monopus),  or  the  feet  may  be  wanting  (sympus 
apus) . 

6.  Hands  or  Feet  Defective. — There  is  a  great  variety  of  malformations  of  the 
hands  and  feet  due  to  arrested  development  of  some  of  the  digits.     The  varia- 
tions include  all  degrees  of  suppression  from  the  shortening  of  a  finger  or  toe  to 
almost  total  absence  of  digits.     Fusions  of  two  or  more  digits  are  not  uncom- 
mon.    Occasionally   a   structure,   suggesting  the  webs  on  the  feet  of  some 
aquatic  animals,  is  present. 

The  condition  known  as  polydactyly  (an  increase  over  the  normal  number 
of  digits)  is  occasionally  met  with.  The  increase  may  range  from  a  partial 
doubling  of  the  distal  segment  of  a  finger  or  toe  to  a  two-fold  quota  of  digits. 
Cases  of  ten  digits  are  extremely  rare,  as  are  even  cases  of  seven  or  eight.  One 
supernumerary  finger  or  toe,  rudimentary  or  complete,  is  not  uncommon.  The 
extra  digits  may  appear  on  a  single  hand  or  foot,  or  on  both  hands  or  feet,  or  on 
all  four  extremities,  not  necessarily  showing  any  symmetry.  A  statement  of  the 
possible  modes  of  origin  of  polydactyly  will  be  found  on  page  213. 

AMNIOTIC  ADHESIONS. — Many  malformations  affecting  the  embryo  or  foetus 
have  been  included  under  this  head.  It  has  been  generally  thought  that  the 
amnion  might  become  attached  to  some  part  of  the  embryo  in  such  a  way  as 
to  cause  malformations  by  interfering  with  the  normal  processes  of  growth. 
The  amnion  might  become  attached  to  the  head  and  by  interfering  with 
normal  growth  produce  hare  lip,  facial  clefts  and  generally  serious  disturb- 
ances. Undue  pressure  on  an  extremity  would  cause  it  to  be  stunted,  or 


612  TEXT-BOOK  OF  EMBRYOLOGY. 

an  encircling  band  of  amniotic  tissue  might  cause  constriction  or  even  ampu- 
tation of  some  of  the  extremities,  or  of  some  of  the  digits.  Under  the  same 
head  there  might  also  be  included  certain  disturbances  possibly  caused  by  the 
umbilical  cord.  The  cord  by  becoming  wound  around  the  neck  or  extremities 
and  interfering  with  development  may  even  cause  the  death  of  the  foetus. 

Causes  Underlying  the  Origin  of  Monsters. 

Within  the  past  century  the  old  grotesque  notions  that  monsters  were  the 
results  of  supernatural  influences  or  of  sexual  congress  with  lower  animals  have 
been  overthrown  as  teratology  has  been  placed  upon  an  embryological  basis. 
The  very  old  belief  that  impressions  on  the  maternal  senses  may  influence  the 
development  of  the  embryo  is  still  held  by  those  who  possess  little  or  no  scien- 
tific knowledge,  and  is  not  uncommon  even  among  gynecologists  and  obstetri- 
cians. While  remarkable  cases  of  coincidence  have  been  recorded,  there  seems 
to  be  no  proof  whatever  that  maternal  impressions  are  reflected  upon  the  child 
in  the  uterus.  On  the  other  hand,  there  has  gradually  accumulated  a  large 
amount  of  negative  evidence  obtained  from  experimental  work.  The  results  of 
this  work  have  been  such  as  to  indicate  that  external  influences — mechanical  or 
physico-chemical — cause  the  production  of  monsters. 

Opposed  to  the  theory  that  monsters  are  due  to  external  influences  is  the 
view  that  their  cause  lies  within  the  germ,  that  is,  that  some  inherent  defect  in 
the  constitution  of  one  or  both  of  the  parental  germ  cells  is  brought  out  in  the 
new  organism  that  develops  after  their  union.  According  to  this  theory, 
therefore,  heredity  is  the  important  factor  in  teratogensis.  While  the  oc- 
currence of  defective  conditions  in  the  germ  cells  cannot  be  demonstrated,  the 
apparent  influence  of  heredity  in  the  production  of  malformations  has  long  been 
recognized.  Certain  malformations,  even  so  great  as  to  put  the  embryo  or 
foetus  in  the  class  of  monsters,  have  been  known  to  occur  in  families  through 
successive  generations.  Such  cases  may  be  mere  coincidences,  yet  more  prob- 
ably they  are  indicative  of  hereditary  influence. 

All  the  theories,  therefore,  are  concerned  with  the  question  "whether  the 
conditions  that  produce  a  monster  are  germinal  and  hereditary  or  are  external  influ- 
ences acting  upon  a  normal  germ"  (Mall).  Some  defend  the  germinal  or 
hereditary  factor  as  the  most  potent  cause  in  the  production  of  malformations, 
while  others  just  as  strongly  advocate  the  view  that  normal  or  abnormal 
development  depends  largely  upon  external  factors.  It  does  not  seem  possible 
to  deny  the  importance  of  heredity  in  the  development  of  the  normal  organism; 
nor,  on  the  other  hand,  can  the  importance  of  external  influence,  of  environ- 
ment, upon  normal  development  be  denied.  The  same  factors  may  be  con- 
sidered as  active  in  abnormal  development,  and  it  does  not  seem  that  either 


TERATOGENESIS.  613 

factor  can  reasonably  be  considered  as  the  only  cause  in  the  production  of 
malformations.  Granting,  however,  that  both  hereditary  and  external  influ- 
ences are  at  work  in  the  production  of  monsters,  it  is  still  difficult  to  determine 
the  separate  role  of  each  factor;  on  the  one  hand,  either  influence  may  appear 
capable  of  having  produced  some  given  anomaly;  on  the  other,  both  of  them 
may  have  been  responsible  for  its  appearance. 

The  first  phase  of  the  theory  of  external  influence  was  presented  three- 
quarters  of  a  century  ago  when  attempts  were  made  to  produce  monsters.  The 
experiments  led  to  the  formulation  of  the  mechanical  theory,  which,  when  applied 
to  human  monsters,  considers  them  as  the  results  of  mechanical  influences  upon 
the  embryo,  such  as  the  pressure  caused  by  tight  lacing  or  by  contractions  of  the 
uterus.  This  theory  was  gradually  transformed  into  the  view  that  amniotic 
bands  compress  or  constrict  the  embryo,  thus  bringing  about  malformations. 
In  its  turn  the  latter  supposition  has  recently  been  criticized  and  the  view  sub- 
stituted that  the  amniotic  adhesions  are  the  results  of  malformations  and  not 
the  cause  of  them  (Mall). 

The  theory  of  external  influence  seems  recently  to  be  losing  ground  in  favor 
of  the  physico-chemical  theory.  The  latter  has  gradually  been  evolved  during 
the  course  of  a  great  number  of  experiments  on  the  production  of  malformations 
and  monsters  among  the  lower  forms  of  animals.  It  has  gained  ground  because 
certain  definite  malformations  have  been  obtained  by  subjecting  the  living  egg 
or  young  embryo  to  unusual  conditions.  The  experiments  consist  of  interfering 
in  some  way  with  the  normal  course  of  development.  The  interference  may  be 
mechanical  or  chemical,  or  both,  but  is  always  of  such  a  nature  as  to  cause  the 
egg  or  embryo  to  develop  under  unnatural  conditions — either  in  an  unnatural 
environment  or  after  having  had  some  of  its  own  substance  wholly  or  partly 
removed.  The  results  obtained,  the  strange  creatures  which  develop  after 
such  interference,  are  not  infrequently  comparable  with  malformations  and 
monsters  found  among  the  higher  animals,  and  they  strongly  suggest  that  mal- 
formations among  the  higher  forms  of  animal  life  are  the  results  of  similar  in- 
terference with  the  normal  course  of  development  of  the  egg. 

THE  PRODUCTION  OF  DUPLICATE  (OR  POLYSOMATOUS)  MONSTERS. — By 
shaking  sea-urchin  ova  when  in  the  two-cell  stage  so  that  the  blastomeres  are 
separated,  each  blastomere  can  be  made  to  grow  into  a  whole  embryo.  De- 
pending upon  the  degree  of  separation,  the  two  embryos  will  be  separate  or  more 
or  less  united  forming  a  double  monster.  If  sea-urchin  ova  are  placed  in  a 
mixture  of  equal  parts  sea-water  and  distilled  water  shortly  after  fertilization, 
the  cell  membranes  rupture  and  part  of  the  protoplasm  bulges  out.  When  the 
ova  are  replaced  in  normal  sea-water  cleavage  begins  and  one  of  the  two  primary 
nuclei  wanders  into  the  extruded  protoplasm.  Each  nucleus  with  its  proto- 
plasm becomes  an  embryo,  and  the  result  is  a  double  monster.  If  the  outflow  of 


614  TEXT-BOOK  OF  EMBRYOLOGY. 

protoplasm  originally  occured  in  several  places,  each  droplet  produces  an 
embryo  and  the  result  is  a  triple  or  quadruple  monster  (Loeb). 

Similar  experiments  have  also  been  performed  on  Vertebrates.  For  example, 
the  two  primary  blastomeres  of  Amphioxus  have  been  partly  separated  and 
double  monsters  developed.  The  blastomeres  in  the  four-cell  stage  have  been 
incompletely  separated,  resulting  in  double  embryos  of  equal  size,  or  triple 
embryos,  or  quadruple  monsters.  Frog's  eggs  have  been  made  to  produce 
double  monsters  by  keeping  them  turned  upside  down  after  the  morula  stage; 
the  same  result  has  also  been  produced  by  loosely  tying  a  ligature  in  the  furrow 
between  the  two  primary  blastomeres.  A  most  curious  result  has  been  obtained 
by  splitting  the  limb  bud  of  a  growing  tadpole  one  or  more  times.  Two  or  even 
a  cluster  of  limbs  may  develop  where  only  one  does  normally  (Tornier). 

These  few  examples  from  the  great  number  of  experiments  which  have  been 
performed  serve  to  show  that  great  light  can  be  thrown  upon  the  problems  of 
teratogenesis  by  experimental  embryology.  While  they  do  not  prove  that  there 
are  no  other  possible  modes  of  origin  for  malformations,  they  indicate  the  im- 
portance of  external  influences  upon  development,  and  afford  tangible  evidence 
in  the  study  of  monsters. 

THE  PRODUCTION  OF  MONSTERS  IN  SINGLE  EMBRYOS. — In  single  embryos 
of  the  lower  forms  it  is  possible  to  produce  by  various  means  a  great  variety  of 
malformations,  many  of  which  are  likewise  comparable  with  malformations 
found  in  human  embryos.  By  placing  recently  fertilized  eggs  of  Fundulus 
in  a  1.5  per  cent,  aqueous  solution  of  potassium  chlorid,  embryos  may  be 
produced  in  which  the  heart  is  developed  but  does  not  beat,  and  in  which  the 
blood  vessels  appear  in  their  normal  positions  but  with  irregular lumina  (Loeb). 
After  extirpating  the  heart  anlage  from  very  young  frog  embryos,  the  latter  grow 
irregularly  and  become  edematous;  the  larger  vascular  trunks  are  distended, 
but  the  capillary  system  is  imperfect  or  absent,  and  the  development  of  many 
other  organs  is  inhibited  (Knower.)  Similar  results  may  be  obtained  by 
placing  the  young  embryos  in  aceton-chloroform  which  inhibits  the  heart 
action. 

It  is  possible  to  produce  typical  spina  bifida  in  frog  embryos  by  putting 
them,  during  the  early  stages  of  development,  into  a  0.6  per  cent,  solution  of 
sodium  chlorid  (Morgan  and  Tsuda).  If  the  eggs  of  Axolotl  are  treated  with 
a  0.7  per  cent,  solution  of  sodium  chlorid  all  the  embryos  have  spina  bifida 
(Hertwig).  If  the  eggs  of  Fundulus  are  placed  in  a  solution  of  magnesium 
chlorid,  50  per  cent,  of  them  produce  embryos  with  cyclopia  (Stockard). 

Even  these  few  examples  from  the  enormous  number  of  experiments  that 
have  been  tried  in  the  study  of  single  monsters  again  lead  to  the  conclusion  that 
at  least  some  malformations  in  single  individuals  are  due  to  external  influences 
and  not  to  germinal  defects. 


TERATOGEXESIS.  615 

THE  SIGNIFICANCE  OF  THE  FOREGOING  IN  EXPLAINING  THE  PRODUCTION 
OF  HUMAN  MONSTERS. — There  is,  of  course,  no  way  to  obtain  experimental 
evidence  for  or  against  any  theory  so  far  as  the  human  subject  is  concerned. 
But  it  is  possible  to  compare  the  results  of  experiments  on  the  lower  animals 
with  condions  found  in  human  embryos.  So  many  malformed  human  embryos 
resemble  in  a  general  way  and  often  in  detail  the  monsters  in  the  lower  forms 
produced  by  experimental  means  that  a  probable  similarity  in  the  causation 
of  them  at  once  suggests  itself.  The  monsters  in  the  lower  forms  are  artifici- 
ally produced  by  interfering  with  the  normal  course  of  development  of  the 
egg,  and  by  disturbing  the  normal  conditions  of  nutrition  and  growth.  The 
disturbing  factors  are  mechanical  or  chemical,  or  both. 

According  to  the  recent  opinion  of  Mall,  the  primary  disturbing  factors  in 
man  are  not  poisons  in  the  maternal  blood,  corresponding  with  chemical  agents 
used  in  experiments,  but  the  faulty  implantation  of  the  ovum  in  the  uterine 
mucosa.  This  means  that,  after  the  fertilized  and  segmenting  ovum  has 
passed  down  the  oviduct  and  entered  the  uterus,  it  fails  to  become  properly 
embedded  in  the  mucous  membrane.  The  immediate  result  is  an  imperfect 
formation  of  the  foetal  coverings,  especially  of  the  chorion. 

The  reasons  for  the  faulty  implantation  are  not  clear,  but  they  are  possibly, 
even  probably,  to  be  found  in  the  condition  of  the  uterus.  The  most  plausible 
explanation  is  that  some  form  of  endometritis  makes  the  uterine  mucosa  in- 
capable of  properly  adapting  itself  for  the  reception  of  the  ovum. 

In  the  case  of  the  human  embryo,  such  an  imperfection  in  the  agency  through 
which  it  receives  its  nourishment  might  be  considered  in  a  sense  analogous  to 
the  external  influences  that  produce  monsters  in  the  lower  forms. 


References  for  Further  Study. 

AHLFELD,  F.:  Die  Missbildungen  des  Menschen.     Leipzig,  1880-1882. 

AHLFELD,  F.:  Lehrbuch  der  Geburtshilfe.     Leipzig,  1903. 

BALLAXTYXE,  J.  W.:  Antenatal  Pathology.  2  Vols.     Edinburgh,  1904. 

BARDEEX,  C.  R.:  Abnormal  Development  of  Toad  Ova  Fertilized  by  Spermatozoa 
exposed  to  the  Roentgen  Rays.  Jour,  of  Exp.  ZooL,  Vol.  IV,  1907. 

BEARD,  J.:  The  Morphological  Continuity  of  the  Germ  Cells  in  Raja  batis.  Anat. 
Anz.,  Bd.  XVIII,  1900. 

COXKLIN,  E.  G.:  The  Cause  of  Inverse  Symmetry.     Anat.  Anz.,  Bd.  XXIII,  1903. 

DARESTE,  C.:  Recherches  sur  la  production  des  monstrosites.     Paris,  1891. 

DRIESCH,  H.:  Entwickelungsmechanische  Studien.  Zeitschr.  /.  wissensch.  Zool.,  Bd. 
LIII,  Bd.  LV. 

FORSTER,:  Die  Missbildungen  des  Menschen.     Jena,  1865. 

HERTWIG,  O.:  Urmund  und  Spina  bifida.     Arch.  /.  mik.  Anat.,  Bd.  XXXIX,  1892. 

HERTWIG,  O.:  Die  Entwickelung  des  Froscheies  unter  dem  Einfluss  schwacherer  und 
starkerer  Kochsalzlosungen.  Arch.  /.  Mik.  Anat.,  Bd.  XLIV,  1895. 


616  TEXT-BOOK  OF  EMBRYOLOGY. 

HERTWIG,  O.:  Missbildungen  und  Mehrfachbildungen.  In  Hertwigs  Handbuch  der 
vergleich.  u.  experiment.  Entwickelungslehre  der  Wirbeltiere,  Bd.  I,  Teil  I,  1903. 

HIRST  AND  PIERSOL:  Human  Monsters.     Philadelphia,  1891. 

KNOWER,  H.  McE.:  Effects  of  Early  Removal  of  the  Heart  and  Arrest  of  the  Circulation 
on  the  Development  of  Frog  Embryos.  Anat.  Record  Vol.  VII,  1907. 

LOEB,  J.:  Beitrage  zur  Entwickelungsmechanik  der  aus  einem  Ei  entstehenden  Doppel- 
bildungen.  Roux's  Arch.  /.  Entwickelungsmechanik  der  Organismen,  Bd.  I,  1895. 

LOEB,  J.:  Studies  in  General  Physiology.     Chicago,  1905. 

MALL,  F.  P.:  A  Study  of  the  Causes  Underlying  the  Origin  of  Iiuman  Monsters.  Jour, 
of  Morphol,  Vol.  XIX,  1908. 

MARCHAND,  L.:  Missbildungen.  In  Eulenburg's  Real -Encyclopedic  der  gesammten 
Heilkunde,  Bd.  XV,  1897. 

MORGAN,  T.  H. :  Half-embryos  and  whole  Embryos  from  one  of  the  first  two  Blastomeres 
of  the  Frog's  Egg.  Anat.  Anz.,  Bd.  X,  1895. 

MORGAN,  T.  H.:  Ten  Studies  in  Roux's  Arch.  j.  Entwickelungsmechanik  der  Organ- 
ismen, Bd.  XV-XIX,  1902-1905. 

PANUM:  Entstehung  der  Missbildungen.     Berlin,  1880. 

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Vol.  VII,  1904. 

SCHULTZE,  O.:  Die  kiinstliche  Erzeugung  von  Doppelbildungen  bei  Froschlarven  mit 
Hilfe  abnormer  Gravitationswirkung.  Roux's  Arch.  /.  Entwickelungsmechanik  der 
Organismen ,  Bd.  I,  1895. 

SCHWALBE,  E.:  Die  Morphologic  der  Missbildungen  des  Menschen  und  der  Thiere. 
Jena,  1906-1907. 

STOCKARD,  C.  R.:  The  Artificial  Reproduction  of  a  Single  Median  Cyclopean  Eye  in 
the  Fish  Embryo  by  Means  of  Sea-water  Solutions  of  Magnesium  Chlorid.  Roux's  Arch,  f 
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TORNIER,    G.:  An  Knoblauchskroten    experimentell    entstandene   iiberzahlige  Hintei 
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WILDER,  H.  H.:  Duplicate  Twins  and  Double  Monsters.     American  Jouc.of  Ana". 
Vol.  Ill,  1904. 

WILLIAMS,  J.  W.:  Obstetrics.     New  York,  1903. 

WILSON,  E.  B.:  On  Multiple  and  Partial  Development  in  Amphioxus.  Anat.  Anz. 
Bd.  VII,  1893. 


INDEX 


Abdominal  cavity,  339,  377 

regions,  defects  of,  610 
Abducens,  VI,  nerve,  462,  464 
Aberrant  ductule,  417 
Abnormal  embryos,  154 
Abrachius,  611 
Acardia,  285,  595 
Acardiaci,  acephali,  596 

acormi,  596 

amorphi,  596 

completi,  596 
Acardiacus,  595 
Accessory  chromosomes,  28,  29 
Achromatic  spindle,  4 
Acini,  the,  443 
Acoustic  area  (see  also  Auditory  area),  558 

ganglion,  588 

VIII,    nerve,    462,    465,    499,    500,    503, 
518,  588 

nerve,  ganglion  cells  of,  589 

radiation,  470,  471 
Acrania,  604,  605,  607 

with  exencephaly,  605 
Acrocephaly,  212 
Acromion  process,  199 
Acrosome,  14 

Acustico-facialis  ganglion,  588 
Acustico-lateral  system, 

influence  on  nervous  system,  446,  459, 466 
Adami,  concerning  hermaphroditism,  435 
Adenoid  tissue,  331 
Adipose  tissue,  167 
Aditus  laryngis,  360,  361 

Afferent  peripheral  neurones,  447,  457,  489  to 
502 

peripheral  nerve  fibers,  451 

root  fibers,  451 
After-birth,  133 

After-brain  (myelencephalon),  455 
Agnathus,  356,  609 

Ahlfeld's   fission   theory   of   symmetrical   du- 
plicity, 599 
Air  sacs,  365 
Ala  cinerea,  527 

magna,  191 

parva,  191 


Alar  plate,  477,  490,  512,  515,  519,  523,  527, 

528 

Albinism,  445 
Albrecht,    concerning    formation    of    incisive 

bone,  196 
Alimentary  tube,  316 

intestinal  region  of,  317 

cesophageal  region  of,  317 

origin  of,  316,  317 

pharyngeal  region  of,  317 

stomach  region  of,  317 

yolk  stalk  of,  317 
Alimentary  tube  and  appended  organs,  316 

anomalies  of,  354 

histogenesis  of  gastrointestinal  tract,  341 
of  liver,  349 
of  pancreas,  353 

intestine,  337 

liver,  345 

mouth,  317 

oesophagus,  335 

pancreas,  350 

pharynx,  329 

salivary  glands,  327 

stomach,  335 

teeth,  322 

tongue,  320 
Alisphenoid  bone,  191 
Allanto-chorion,  102 
Allantoic  blood-vessels,  in  Mammals,  104 

duct,  114,  337 

sac,  104 
Allantois,  the,  102 

blood-vessels  of,  in  chick,  103 
in  Mammals,  109 
in  man,  115 

functions  of,  in  chick,  102 
in  man,  114 

in  Mammals,  107 

in  man,  114 

relation  of,  to  chorion,  102 
Allen,  concerning  sex  cells,  404 
Alopecia,  445 
Alternation  of  vertebrae  and  myotomes,  180, 

295 

Amelus,  611 
617 


618 


INDEX 


Amitosis,  3 

diagram  showing,  4 
Amnion,  false,  98 

formation  from  amniotic  fold,  97 

in  Birds,  95 

in  Mammals,  104,  106 

in  man,  in 

in  Reptiles,  95 

rhythmical  contractions  of,  98,  114 
Amniotic  adhesions,  611 

cavity,  64,  97,  in,  133 

fluid,  112 

folds,  96 

in  MammalyTnfy  ~ 

suture,  96 

Amoeboid  movement  of  nuclei,  2 
Amphiaster,  4,  33 
Amphibians,  cleavage  in,  42,  43 

gastrulation  in,  52 

mesoderm  formation  in,  72 
Amphicytes,  492 
Amphimixis,  38 
Amphioxus,  cleavage  in,  41 

gastrulation  in,  51 

germ  layers  of,  71 

mesoderm  formation  in,  68 
Ampullae  of  semicircular  canal,  583,  588 
Amyelus,  606 
Anal  membrane,  341 

opening,  341 

pit,  34i 
Anaphase,  6 
Anencephaly,  313,  608 
Angioblast,  269 
Angiomata,  445 

Angle  of  the  mouth,  141,  148,  318 
Angulus  praethalamicus,  537,  540,  547 
Ankyloblepharon,  608 
Animal  pole  (micromere),  52 
Animalculists,  XIII 
Annular  placenta,  130 
Anomalies,  see  also  Terato genesis 

of  the  alimentary  tract,  354 

of  the  diaphragm,  382 

of  the  large  vascular  trunks,  287 

of  the  heart,  285 

of  the  integumentary  system,  444 

of  the  mesenteries,  382 

of  the  muscular  system,  313 

of  the  nervous  system,  560 

of  the  omenta,  382 

of  the  pericardium,  382 

of  the  placenta,  130 


Anomalies,  of  the  respiratory  system,  364 

of  the  skeletal  system,  209 

of  the  umbilical  cord,  131 

of  the  urogenital  system,  429 

of  the  vascular  system,  285 
Anomalous  position  of  the  heart,  285 

Anophthalmia,  608          , 

Anterior  colliculi,  see  Anterior   corpora   quad- 

rigemina 
Anterior  (cerebral)  commissure,  454 

commissure  of  the  cord,  503,  507 

corpora  quadrigemina,  467,  517,  530,  533, 
576 

horn  (ventral  gray  column),  507 

neuropore,  451 

perforated  space,  541 
Anthelix,  591 
Antitragus,  591 
Aorta,  dorsal,  218,  240 
Aortae,  primitive,  218 
Aortic  arches,  219,  241 
Apathy,  concerning  peripheral  nerves,  494 
Apical  body,  14 
Apolar  cells,  484 

Appendage  of  the  epididymis,  416 
Appendicular  skeleton,  198 

anomalies  of,  212 

derivation  of,  199 
Appendix  testis,  421 

vermiform,  341 
Aprosopus,  608 
Apus,  6n 

Aquaeductus  Sylvii,  456 
Arch  of  the  aorta,  242 
Archencephalon,  453 
Archenteron,  51,  56 

of  Amphibians,  53 

of  Amphioxus,  5' 

of  Birds,  63 

of  Reptiles,  61 
Archipallial  commissure,  see  Fornix 

commissure 
Archipallium,  468,  505,  537,  541,  546  to  552 

connections  of,  505,  537,  558 
Arcuate  fibers  (external),  515 

(internal),  508,  515 
Arcus  aortae,  242 
Area  opaca,  61 

pellucida,  61,  79 

of  supplemental  cleavage.  60 

vasculosa,  79,  101,  217 
Areola,  the,  443 
Areolar  tissue,  167 


INDEX 


619 


Arm,  development  of,  150 
Arrectores  pilorum,  438 
Arteria  centralis  retinae,  569 
Arteries,  240 

allantoic,  222,  241 

anomalies  of,  287 

basilar,  243 

brachial,  248 

carotid,  242 

cerebral,  245 

coeliac,  246 

epigastric,  245 

femoral,  249 

gastric,  246 

gluteal,  250 

hepatic,  246 

hyaloid,  569 

hypogastric,  248 

iliac,  247,  248 

innominate,  243 

intercostal,  245 

internal  spermatic,  247 

lumbar,  245 

mammary,  245 

median,  248 

mesenteric,  246 

omphalomesenteric,  101,  103,  218,  246 

ovarian,  247 

peroneal,  250 

popliteal,  249 

pulmonary,  235,  243 

radial.  249 

renal,  247 

saphenous,  249 

sciatic,  249 

splenic,  246 

subclavian,  242,  244,  248 

testicular,  247 

tibial,  250 

ulnar,  248 

umbilical,  103,  222,  241 

vertebral,  244 

vesical,  248 

vitelline,  101,  103,  218,  241 

volar  interosseous,  248 
Articular  cavity,  206 
Aryepiglottic  ridges,  361 
Arytenoid  ridge,  361 

Ascaris   megalocephala,    for    study   of   matu- 
ration, 17 

Assheton,  concerning  origin  of  parasitic  duplic- 
ity, 603 
Aster,  2,  3,  7 


Astomus,  609 
Astragalus,  the,  204 
Asymmetrical  duplicity,  610 

origin  of,  602 

parasitic  structures  in  the  sexual  glands, 

601 

Atlas,  the,  184 
Atresia  of  the  anus,  357 

oris,  609 
Atria  of  heart,  231 

of  lungs,  365 
Atrial  septum,  233 
Atrio-ventricular  canal,  233 
Atrium  of  inner  ear,  583 
Attraction  cone,  36 

sphere,  2,  3,  4 
Auditory  area  of  pallium,  470,  557,  558 

meatus,  external,  origin  of,  143,  147,  591 

nerve,  see  Acoustic  VIII 

ossicles,  derivation  of,  197,  589 

pit,  582 

placode,  582 

vesicle,  582 

Auerbach,  plexus  of,  491 
Aula,  542 
Auricle,  590 

Autonomic  system  (sympathetic),  458 
Autosite,  600 
Axial  filament,  14,  20,  21 

skeleton,  178 

anomalies  of,  209 
head,  186 
notochord,  178 
primitive,  178 
ribs,  184 
sternum,  185 
vertebrae,  179 

thread,  14 

Axis,  (epistropheus),  184 
Axone,  the,  478,  485 

Balfour,  concerning  peripheral  nerves,  493 

Bardeen,  concerning  peripheral  nerves,  493 

Bartholin's  glands,  403 

Basal  plate,  125,  477,  502,  507,  512,  514,  524 

Basilar  artery,  243 

Basioccipital  bone,  190 

Basisphenoid  bone,  191 

Basket  cells,  529 

Baskets,  529 

Beard,  concerning  sex  cells,  404 

Bechterew,  v.,  central  tegmental  tract  of,  519 

Belly  stalk,  92,  114,  136 


620 


INDEX 


Bertini,  columns  of,  397 
Bicornuate  uterus,  433 
Bielschowsky,  method  of  staining,  563 
Bilateral  hermaphroditism,  434 
Bile  capillary,  349 
Bipartite  uterus,  433 
Birds,  cleavage  in,  45 

gastrulation  in,  57 

mesoderm  formation  in,  74 
Bischoff,  concerning  origin  of  parasitic  duplic- 
ity, 603 
Bladder  (see  also  Urinary  Bladder),  400 

anomalies  of,  431 
Blastema,  metanephric,  392 
Blastemal  stage,  180 
Blastocyst,  49 
Blastoderm,  57,  59,  133 
Blastodermic  vesicle,  134 
Blastomeres,  40 
Blastopore,  51 

(crescentic  groove),  59 
Blastula,  47,  133 
Blood,  cells  of,  267 

relation  of  maternal  and  foetal  blood  in 

Mammals,  109 
in  man,  115,  127 
Blood  cells,  development  of,  267 

erythroblasts,  270 

erythrocytes,  270 

haemoblasts,  268 

histogenesis  of,  267 

leucocytes,  270 

lymphoblasts,  268 

lymphocytes,  270 

megaloblasts,  270 

mesamceboid,  269 

mononuclear  leucocytes,  270 

normoblasts,  270 

primitive,  217,  268 
lymphocytes,  268,  269 

table  showing  development  of,  273 
Blood  islands,  217,  268 
Blood  plates,  273 
Blood  vascular  system,  216 
Blood  vessels,  allantoic,  function  of,  104 

arteries,  240 

factors  in  development  of,  226 

heart,  227 

origin  of,  224 

placental,  127 

sinusoids,  260 

veins,  250 
Blue  babies,  287 


Body  cavity,  see  Ccelom 
Bone,  compact,  172 

diaphysis  of,  176 

epiphysis,  176 

growth  of,  176 

intracartilaginous,  172 

shaft  of,  176 

spongy,  171 

subperiosteal,  172 
Bone  cells,  171 

destroyers,  171 

formers,  171 

marrow,  177 
Bones,  defective  or  absent,  6n 

derived  from  the  branchial  arches,  194 

membrane,  of  the  skull,  192 
Bonnet,   concerning   derivation  of  pigmented 
layer  of  retina,  577 

concerning  double  origin  of  vitreous,  575 

concerning  the  Erganzungshohle,  55,  56 

concerning  the  Erganzungsplatte,  56 

concerning  gastrulation,  51 

concerning  origin  of  parasitic  duplicity,  603 

concerning  the  primitive  intestinal  cord,  62 

concerning  the  primitive  streak,  61 
Born,  concerning  potentiality  of  germ  cells,  604 
Boveri,  concerning  the  "dynamic  center"  of 

the  cell,  8 

Bowman,  membrane  of,  578 
Bowman's  capsule,  387,  395 
Brachia,  anterior,  530,  533 
Brain,  the,  453,  473 

after-brain  (myelencephalon),  455 

aquaeductus  Sylvii,  456 

archencephalon,  453 

cephalic  flexure  of,  454 

cerebellum,  455,  477,  512,  525 

corpora  striata,  455,  467,  474,  478,  539,  54* 

defects  in,  604,  605 

deuterencephalon,  453 

diencephalon,  455,  467,  474,  478,  531 

distinguishing    features    of    human    and 
their  biological  significance,  468,  470 

end-brain  (telencephalon),  455 

epichordal  part  of,  453,  457 
segment  al,  512 

fore-brain  (.prosencephalon),  454 

hind-brain  (metencephalon),  455 

inter-brain  (diencephalon),  455 

isthmus,  455,  513 

medulla  oblongata,  477,  512 

mid-brain  (mesencephalon),  454 

plica  encephali  ventralis,  453 


INDEX 


621 


Brain,  plicarhombo-mesencephalica,  475 
prechordal  part,  453,  457 
rhinencephalon,  455,  467,    505, -537,  54° 

to  541 

rhombic  (rhombencephalon),  454 
rhombo-mesencephalic  fold  of,  454 
segmental,  457 

character  of,  456,  457 
telencephalon,  455,  467,  538,  to  561 
ventral  cephalic  fold,  453 
ventricles  of,  456,  478,  542 
Branchial  arches,  malformations  of,  608 
arches,  origin  of,  140,  146 
cysts,  6io 

epithelial  bodies,  331 
glomus  caroticum,  335 
parathyreoids,  332 
thymus,  333 
thyreoid  gland,  331 
grooves,  origin  of,  140,  146 
Branchiogenetic  cysts,  610 
Branchiomeric  muscles,  302 
segmentation,  460,  489 
Brachium,    conjunctivum,    see   Superior   cere- 

bellar  peduncle 

pontis,     see     Middle    cerebellar    peduncle 
quadrigeminum  inferius,  471 
Brandt,  concerning  anomalies  of  hair,  445 
Bremer,  concerning  spinal  accessory  nerve,  496 
Brodmann,  concerning  cortical  layers,  556 
Bronchial  rami,  364 
Brunner,  glands  of,  343 

Bryce-Teacher's  ovum,   86,  90,   92,    in,   117 
Bucco-nasal  membrane,  580 
Burdach,  columns  of,  459,  471,  518 

nuclei  of  the  columns  of,  459,  466,  467, 

520 
Bursa  pharyngea,  331 

Caecum,  the,  337,  340 

Cajal,    concerning   development   of   cerebellar 
cells,  548 

concerning  neurofibrils  and  early  develop- 
ment of  nerve  cells,  484,  485 

concerning  optic  nerve,  576 

concerning  peripheral  nerves,  494 
Calcaneus  (os  calcis),  204 
Calcar  avis,  553 
Calcarine  area,  470 
Calcification  centers,  169,  173 

zone,  172,  174 
Calyces,  393 
Campbell,  concerning  cortical  areas,  559 


Canal  of  Cloquet,  576 

of  Petit,  578 
Canalized  fibrin,  122 
Canals  of  Gartner,  416 
Capillaries,  villous,  127 
Capitulum  of  rib,  185 
Capsule  of  Glisson,  346,  374 
Carotid  arteries,  242 

gland,  429 

skein,  429 
Carpal  bones,  200 

Carpenter,  concerning  ciliary  ganglia,  501 
Cartilage,  168 

cuboid,  204 

cuneiform,  204 

episternal,  185 

ethmoidal,  192 

laryngeal,  362 

MeckePs,  189,  194 

of  hip  bone,  203 

thyreoid,  362 

triticeous,  362 

Wrisberg's,  363 
Cartilaginous  primordial  cranium,  188 

stage,  1 80 
Cauda  equina,  512 
Caudal  gut,  342 

lymph  sac,  275,  279 
"Caul,"  113 
Cavity,  abdominal,  377 

amniotic,  64 

body,  370 

completion,  55,  56,  59 

extraembryonic  body,  92,  370 

invagination,  59 

parietal,  227,  372 

pericardial,  370,  371 

peritoneal,  370,  373 

pleural,  370,  373 

primitive  pericardial,  84,  227,  230,  371 

segmentation,  47,  54,  59 
Cell,  the  typical  animal,  i 

centrosome  of,  i,  3 

diagram  of,  2 

functions  of,  3 

nucleus  of,  i 

structure  of,  i 
Cell  division,  3 

direct  or  amitosis,  3 

indirect,  or  mitosis,  4 

references  for  further  study  of,  9 
Cell  migration,  of  nervous  system,  478, 
479,  484,  485,  486,  519,  527 


622 


INDEX 


Cell-plate,  8 

Cell  proliferation,  479,  514,  519,  527 

in  neural  tube,  479 
Cells,  air,  365 

apolar  of  neural  tube,  484 

association,  457,  468,  528,  558,  530,  558 

basket,  529 

bipolar  of  neural  tube,  484 
of  retina,  573 

blood,  267 

bone,  171,  174 

chromaffin,  426 

cochlear  ganglion,  589 

cone,  501,  505,  572,  573 

daughter,  3 

decidual,  123 

dermal,  442 

ependyma,  481,  483 

epithelial,  479 

fat,  1 68 

female  germ,  21 

follicular,  408 

germ,  10 

germinal  of  neural  tube,  479,  483 

giant,  177 

granule,  548 

hair,  586,  588,  589 

heart-muscle,  293,  312 

Hensen's,  588 

indifferent,  404 

of  neutral  tube,  484 

interstitial,  412 

liver,  349 

lutein,  31, 

lymphoid,  335 

male  germ,  21,  25 

mastoid,  590 

mesodermal,  370,  438 

mitral,  505 

monopolar,  485 

Miiller's,  572 

myelocytes,  178,  272 

myoblasts,  307 

neuroglia,  481,  483 

odontoblasts,  325 

of  Sertoli,  17,  21 

osteoblasts,  171 

osteoclasts,  171 

phaeochrome,  426 

pillar,  588 

polymorphous,  557 

Purkinje,  527 

pyramid,  555,  556,  558 


Cells,  rod,  501,  505,  572,  573 

sex,  404 

solitary,  of  Meynert,  558 

somatic,  101 

spermatids,  17,  19,  28 

spermatocytes,  17 

spermatogenic,  17 

spermatogonia,  17,  24 

supporting,  17,  21 

sustentacular,  572 

vestibular  ganglion,  589 

wandering,  354 

yolk,  53 

(or  merocytes),  59 
Cement  substance,  origin  of,  165 
Central  canal,  509 

spindle,  4 

fibei  s  of,  6 
Centralis,  526 

Centriole,  the,  2,  3,  4,  5,  6,  7,  8 
Centrolecithal  ova,  44 
Centrosome,  the,  3,  8,  19 

in  fertilization,  34 
Centrosphere,  3,  4 
Cephalic  flexure,  139,  454,  473 
Cephalization,  450 
Cephalocele,  605 
Cephalopagus,  598 
Cephalothoracopagus  diprosopus,  597 

janiceps,  598 

Cerebellar  hemispheres,  472,  526 
Cerebellum,  455,  457,  466,  512,  525 

afferent  connections  of,  466 

basket  cells  of,  529 

cells  of  Purkinje,  527,  529 

centripetal  fibers  of,  529 

climbing  fibers  of,  530 

cortex  of,  527 

efferent  connections  of,  466 

flocculi,  526 

granular  layer  of,  527 

granule  cells  of,  528 

hemispheres  of,  472,  526 

lobes  of,  526 

middle  peduncle  of,  466,  472 

molecular  (plexiform)  layer,  527 

mossy  fibers,  530 

nodule,  526 

parallel  fibers  of,  528 

peduncles  of,  466,  471,  473,  523,  530 

postnatal  development,  528,  529 

superior  peduncle  of,  466 

taenia  of,  513 


INDEX 


623 


Cerebellum,  velum  of,  513 

vermis  of,  526 

Cerebral  hemispheres  (see  also  Pallium),  457, 
470,  474,  538,  541  to  560 

hernia,  605 

Cerebrospinal  ganglia,  451 
Cervical  depression,  142 

enlargement,  459 

fistulae,  complete,  609 
incomplete,  609 

flexure,  140,  478 
Cervix,  the,  415 

plicae  palmatae  of,  415 
Chalaza,  13 

Cheilognathoprosoposchisis,  609 
Cheilognathoschisis,  609 
Cheilognathouranoschisis,  609 
Cheiloschisis,  609 

Chiari,  concerning  sebaceous  cysts,  445 
Chiasma  eminence,  454 
Chin,  origin  of,  144 
Choanen,  primitive,  580 

Chondrification  first  occurrence  in  head  skele- 
ton, 1 88 
Chondrocranium,  189 

ossification  of,  190 
Chorda  (see  also  Notochord),  68 

anlage,  87 

dorsalis,  178 

tympani,  462,  498 
Chordae  tendinae,  237 
Chordal  plate,  68 

sheath,  178 

Chorio  epitheliomata,  432 
Chorioid,  defective  pigmentation  of,  445 

fissure,  of  pallium,  547 

fold,  547 

of  rhombencephalon,  543 

of  eye,  575 

plexus  of  fourth  ventricle,  453,  513,  525 
of  lateral  ventricle,  453,  533,  543,  547 
of  third  ventricle,  453,  533 
Chorioidal  fissure  of  eye,  567,  575 
Chorion,  in  chick,  103 

in  Mammals,  104,  106 

in  man,  115,  135 

primitive,  98 
function  of,  103 

relation  of,  to  allantois,  115 
Chorion  frondosum,  118,  120 

laeve,  118,  120 
Chorionic  villi,  no,  118 

in  von  Spec's  embryo,  88 


Chromaffin  cells,  426 

granules,  426 
Chromatin,  i 

Chromophilic  bodies,  478,  489 
Chromosomes,  5,  6,  7 

accessory,  28,  29 

diploid  number  of,  17,  22,  24 

haploid  number  of,  18,  22 

identity  of,  7,  26 

qualitative  differences  in,  26 

synapsis  of,  18,  22,  26 

U  or  V  shaped,  5,  6 
Chryptorchism,  432 
Cilia,  of  the  cells  of  gastrula,  51 
Ciliary  body  of  eye,  577 

ganglion,  501 
Circulation,  changes  in,  at  birth,  265 

allantoic,  223,  240 

foetal,  course  of,  265 

reversal  of,  595 

vitelline,  220 
Circulus  arteriosus,  243 
Cisterna  chyli,  275 
Clark,   W.    C.,   concerning   the  joint   capsule 

and  cavity,  209 
Clarke's  columns,  466,  511 
Clava,  524 
Clavicle,  200 
Cleavage  (segmentation),  40 

discoidal,  40,  45,  47 

equal,  40,  41 

forms  of,  40 

holoblastic,  40,  41,  46 

meroblastic,  40,  44 

in  Amphioxus,  41 

in  Birds,  45 

in  the  frog,  42,  43 

in  Mammals,  48 

in  man,  85 

in  Synapta,  41 

of  ova  of  opossum,  49 
of  rat,  50 

references  for  further  study  of,  50 

superficial,  40,  44 

unequal,  40,  42 
Cleft  palate,  212,  608,  609 
Climbing  fibers,  530 
Clitoris,  the,  424 
Cloaca,  the,  341,  400 

persistence  of,  357 
Cloacal  membrane,  400 
Closed  skein,  5 
Closing  plate,  125 


624 


INDEX 


Coccygeal  gland,  285 
Cochlea,  460,  467 
Cochlear  ganglion  cells,  589 
of  VIII  nerve,  499 

part  of  acoustic  (auditory)  nerve,  462 
pouch,  583 
terminal  nuclei,  466 
Coelenteron  (see  also  Archenterori) ,  51 
Coelom  (myocoel),  70,  370 

embryonic,  370 
Collaterals,  504,  529,  556 
Colloid  secretion  of  thyreoid  gland,  331 
Colon,  the,  338 
ascending,  34<y 
descending,  340 
sigmoid,  340 
transverse,  340 
Colostrum  corpuscles,  444 
Column  cells,  503 
heteromeric,  503 
tautomeric,  503 
Columns,  anterior  white,  507 

dorsal  gray  (posterior  horn)  458,  507 
posterior  white,  490,  503,  507 
Columns  of  Bertini,  397 

of  Burdach,  459,  471,  418 

nuclei  of,  459,  471,  520 

of  Goll,  459,  471,  510,  518 

nuclei  of,  459,  471,  520 

Commissura  habenularis,  455,  538 

mollis  (see  Massa  intermedia'),  535 
Commissural  column  cells,  503 
Commissure,  anterior,  (cerebral),  454 
neopallial,  468 
posterior,  454,  533,  538 
Completion  cavity  (see  also  Erganzungshohle), 

55,  56 
plate  (see  also  Erganzungsplatte),  56,  59, 

68 

Concha,  144,  147 
Conchae,  inferior,  192 
middle,  192 
superior,  192 
Cones,  501,  505,  572,  573 
Confluens  sinuum,  252 
Conjugation,  38 
Connective  tissue  follicle,  440 
tissues,  the  161 
adipose,  167 
areolar,  167 
cartilage,  168 
development  of  the,  161 
embryonic,  167 


Connective  tissues,  fibers  of,  166 
fibrillar  forms,  166 
ground  substance  of,  166 
histogenesis  of,  163 
intermuscular,  310 
osseous,  169 
osteogenetic,  171 
periosteum,  171 
Contractile  fibrils,  294 
Contractions,  rhythmical,   of  the  amnion,  in 

man,  112 

Convolutions  of  cerebral  hemispheres,  542 
Coordinating    centers,    higher,    see    Supraseg- 

mental  structures 
Coordination,  447 
Coracoid  process,  199 
Cords,  medullary,  406 
Pfliiger's  egg,  408 
rete,  404 
sex,  405,  406 
Cornea,  578 

elastic  membranes  of,  578 
endothelium  of  Descemet,  578 
membrane  of  Bowman,  578 
substantia  propria  corner,  578 
Cornu  ammonis,  548,  552 
Corona  radiata,  n 

of  cerebral  hemispheres,  537 
Coronoid  process,  196 
Corpora  quadrigemina,  467,  517,  530 
anteria  brachia  of,  530 
layers  of,  530 
Corpus  albicans,  31 

callosum,  468,  543,  550,  558 
genu  of,  551 
splenium  of,  551 
haemorrhagicum,  30 
luteum,  31 
changes  in,  32 
false,  32 

of  pregnancy,  32 
true,  32 

Luysii,  537,  538 
sterni,  186 

striatum,  455,  467,  477,  478,  539,  541 
crura  of,  539,  541,  543 
tail  (cauda),  543 

Correns,  concerning  determination  of  sex,  435 
Cortex,  cerebral,  554 
Cortical  layer  of  telencephalon,  542 
Cortico-pontile  fibers  (of  the  pes),  466,  471, 

472,  524,  558 
Cord's  organ,  460,  467,  558,  587 


INDEX 


625 


Costal  process,  180 

Cotyledon  (lobe),  127 

Cotyledons,  123 

Covering  layer  of  blastula   (trophoderm)   (see 

also  Enveloping  layer),  48 
Cowper's  glands,  403 
Cranial  cavity,  development  of,  171 
Craniopagus,  598 

parasiticus,  598 
Craniorachischisis,  606 
Cranior-rachischisis,  604 
Cranioschisis,  604,  607 
Crescentic  form  of  embryo,  140,  143 

groove,  of  Reptiles,  59 
Crescents  of  Gianuzzi,  329 
Cribriform  plate,  192 
Cricroid  cartilage,  197 
Crista  ampullaris,  586,  589 

galli,  192 

Crown-rump  length,  153 
Crusta,  see  Pes  pedunculi 
Cryptophthalmia,  608 
Cuboid  cartilage,  204 
Culmen,  526 
Cumulus  ovigerus,  410 
Cuneiform  cartilages,  204 

ridge,  361 
Cuneus  of  cerebral  hemispheres,  554 

of  medulla,  524 
Cutis  plate,  71,  163,  164,  293 
Cuvier,  ducts  of,  222,  251,  253 
Cyclocephaly,  608 
Cyclopia,  560,  589,  598,  608 
Cyclostomus,  608 
Cyclotus,  608 

Cylinder  furrow  of  His,  509 
Cylindrical  form  of  body,  137 
Cystadenomata,  433 
Cystic  tumors,  60 1 
Cysts,  432, 

dermoid,  445 

sebaceous,  445 
Cytoplasmic  plate,  8 
Cyto-trophoderm,  117,  121,  122 

Darkschewitsch,  nucleus  of,  517 
Daughter  cells,  3 

nuclei,  4,  6 
Decidua,  116 

basalis,  120 

capsularis,  119 

parietalis,  119 
Decidual  cells,  123 


Decussation  of  Forel,  517 

of  Meynert,  530 
DeFormatione  Foetus,  XIII 
De  Formato  Fcetu,  XIII 
de  Graaf,  Regnier,  XIII 
de   Graaf,   Regnier,  concerning    the    Graafian 

follicle,  XIII 

Deiter's  nucleus,  tracts  from  466,  511,  517 
Dendrites,  485 

apical,  555 

of  pyramidal  cells,  556 
Dens,  the  (odontoid  process),  184 
Dental  groove,  323 

papilla,  323 

sac,  326 

shelf,  323 
Dentinal  canals,  326 

fibers,  326 

pulp,  323,  325 
Dentine,  32.3,  325 

formation,  326 
Dermal  navel,  101,  112 

umbilicus,  101 
Dennis,  the,  438 

arrectores  pilorum,  438 

pigment  of,  438 

tactile  corpuscles  of  Meissner  of,  438 

tunica  dartos,  438 
Dermoid  cysts,  445,  601 
Descemet,  membrane  of,  578 
Descent  of  ovary,  422,  437 

of  testicle,  419,  437 
Determination  of  sex,  27 
Deuterencephalon,  453 
Deutoplasm,  i,  12,  13 
Dextrocardia,  286,  355 
Diaphragm,  the,  370,  375 

anomalies  of,  382 

caudal  migration  of,  376 

changes  in  position  of,  376 

ligaments  of,  376 

muscular  elements  of,  300 

primary,  374 

Diaphragmatic  hernia,  382 
Diaphysis,  176 
Diaplexus,  533 
Diarthrosis,  207 
Diastematomyelia,  606 
Diaster,  6 
Diatela,  533 
Dibrachius,  597 
Dicephalus,  598 
Didelphys,  uterus,  433 


626 


INDEX 


Diencephalon  (inter-brain),  84,  455,  467,  474, 
478,  531  to  538 

epithalamus,  467,  468,  505,  536 

hypophysis,  467,  533 

hypothalamus,  467,  468,  478,  531,  533 

nuclei  of,  467 

Rathke's  pouch,  531 

sulcus  hypothalamicus,  531 
Monroi,  531 

thalamus,  467,  478,  505,  536 
Diffuse  nucleus,  2 
Digits,  beginnings  of,  143 

defects  or  absence  of,  611 
Diploid  number  of  chromosomes,  17,  22,  24 
Diprosopus,  598 

diophthalmus,  598 

monostomus,  598 

tetrophthalmus,  598 

triophthalmus,  598 
Dipygus  parasiticus,  597 
Discoidal  placenta,  no 
Disse,  concerning  olfactory  nerve,  581 
Diverticulum  of  Nuck,  422 
Dollinger,  XIII 
Dorsal  flexure,  139 

mesogastrium,  378 

septum  of  spinal  cord,  510 
Dorso-,  lateral  plate,  see  Alar  plate 
Double  heart,  286 
Driesch,  concerning  potentiality  of  germ  cells 

604 

"Dry"  labor,  113 
Ducts,  allantoic,  114,  337 

alveolar,  365 

cochlear,  586 

Cuvier's,  222,  251,  253,  373 

cystic,  346 

deferent,  416 

ejaculatory,  416 

endolymphatic,  583 

hepatic,  346 

lacrymal,  579 

mesonephric,  386,  400 

Miillerian,  399,  413,  417 

of  the  epididymis,  416 

oviduct,  414 

pronephric,  384,  385 

reuniens,  586 

Santorini's,  3*51 

seminiferous,  402 

Steno's,  327 

thoracic,  275,  279 

thyreoglossal,  331 


Ducts,  utriculosaccular,  586 

Wharton's,  328 

Wirsung's  351 

Wolffian,  386 
Ductule,  aberrant,  417 

efferent,  417 
Ductus  arteriosus,  238,  243,  267 

choledochus,  346 

pleuro-pericardiacus,  372 

venosus,  256,  260 
Duodenum,  the,  337,  338 

change  of  position  of,  380 
Duplicate  monsters,  593 

asymmetrical  duplicity,  600 

Marchand's  scheme  of,  593 

symmetrical  duplicity,  594 

teratoid  tumors,  594 

true  parasitic  duplicity,  600 
Duplicity  incomplete,  598 
Duval,     concerning    formation    of    primitive 

streak,  61 
Dyads,  18,  22 
Dynamic  center,  8 

Ear,  450,  457,  462,  467,  506,  582 
anomalies  of,  591,  609 
cochlea,  460 

Corti's  organ,  460,  467,  558,  587 
external,  582,  590 
internal,  582 
labyrinth,  460 
middle,  582,  589 
Ear,  inner, 

acoustic  nerve,  588 
atrium,  583 
auditory  pit,  582 

placode,  582 

vesicle  (otocyst),  582,  583 
cells  of,  588 
cochlear  pouch,  583 
ducts  of,  586 

endolymphatic  appendage  of,  583 
fenestra  cochleae  (rotunda),  587 

vestibuli  (ovalis),  587 
membrana  tectoria,  588 
organ  of  Corti,  587 
perilymph,  586 
perilymphatic  space,  586 
saccule,  586 
scala  media,  586,  587 

tympani,  586,  587 

vestibuli,  586,  587 
semicircular  canals  of,  583 


INDEX 


627 


Ear,  inner,  spiral  lamina,  587 

utricle,  586 

vestibular  membrane  (of  Reissner),  587 

pouch,  583 
Ear,  middle,  589 

Eustachian  tube,  590 

incus,  589 

malleus,  589 

mastoid  cells,  590 

stapes,  589 
Ear,  outer,  590 

anthelix,  591 

antitragus,  591 

auricle,  591 

external  auditory  meatus,  590 

helix,  591 

lobule,  591 

tragus,  591 

tubercles  of,  591 

tympanum,  591 
Ectoderm  (epiblast),  51,  133 

formation  of,  51 

in  Amphibians,  54 

in  Amphioxus,  51,  52 

in  Birds,  60,  62 

in  frog,  56 

in  Mammals,  64 

in  Triton,  53,  54 

in  Reptiles,  58 
Ectopia  cordis,  211,  286,  382,  610 

vesicae,  610 

viscerum,  610 

of  the  kidneys,  429 
Ectopic  gestation,  30 
Ectoplasm,  170 

Edinger,  concerning  the  oral  sense,  468 
Effectors,  448,  451,  457 
Efferent  ductules,  416 

peripheral  nerve  fibers,  452 

peripheral  neurones,  447,  457,  486  to  489 

root  fibers,  486 
Egg  (see  also  ovum),  10 

cleavage  in  hen's,  45 

diagram  of  hen's,  13 

nests,  408 

cords,  Pfiuger's,  408 
protoplasm,  n 
Eggs,  centrolecithal,  44 

meiolecithal,  12 

mesolecithal,  12 

polylecithal,  12 

tetolecithal,  12 
Eigenmann,  concerning  sex  cells,  404 


Ejaculatory  duct,  416 

Embryonal  bud  (inner  cell-mass),  64 

Embryonic  ccelom,  370 

connective  tissue,  167 

disk  (see  also  Germ  disk),  134,  135 
Embryos,  abnormal,  154 

age  and  length  of,  151 

conclusions  of  His,  concerning  age  of,  151 

gross  anomalies  of,  155 

Mall's  formula?  for  deducing  age  of,  153 

normal,  154 

pathological,  154 

relation  of  age  to  length,  153 

transparency  of,  155 
Enamel  organ,  323 

prisms,  324 

pulp,  324 

Encephalocele,  605 
Encranius,  600 

End-brain  (telencephalon),  455,  467,  538  to  561 
End  disk,  14 

kmob,  anterior,  14,  20 

posterior,  14,  20 

ring,  14 

Endocardium,  origin  of,  227 
Endolymphatic  duct,  583 

sac,  583 

Endomysium,  311 
Endothelium,  217,  268 
Engastric  (intraabdominal)  parasites,  601 
Entoderm  (hypoblast),  51 

formation  of,  51 

of  Amphibians,  54,  56 

of  Amphioxus,  51 

of  Birds,  58,  59,  60 

of  Mammals,  64 

of  man,  87,  90 

of  Reptiles,  58,  59,  60 

primitive,  133 

yolk,  54 

Entodermal  tube,  316 
Entrance  plug,  116 
Enveloping  layer,  see  Covering  layer  (tropho- 

derm),  133 

Eparterial  bronchial  ramus,  365,  368 
Ependyma  cells,  481 
Epiblast  (see  also  Ectoderm),  51 
Epicanthus,  608 

Epichordal  brain,  lateral  series  of  nuclei  of, 
487,  488 

medial  series  of  nuclei  of,  487,  488 
Epichordal  segmental  brain  and  nerves,  457, 
459 


628 


INDEX 


Epicondyles,  200 
Epidermis,  the,  71,  437 

epitrichium  of,  437 

periderm  of,  437 

stratum  corneum,  438 

germinativum  of,  437 
granulosum,  437 
lucidum,  438 
Epididymis,  anomalies  of,  432 

appendage  of  the,  416 

duct  of,  416 

Epigamous  determination  of  sex,  412 
Epigenesis,  doctrine  of,  XIII 
Epiglottis,  361 
Epignathus,  600,  602 
Epimysium,  311 
Epiphyses  of  vertebrae,  183 
Epiphysis  of  bone,  176 

(pineal  body),  454,  467,  533 
Epiploic  foramen,  378 
Epispadias,  432 
Episternal  cartilages,  185 
Epistropheus,  the  (axis),  184 
Epithalamic  region,  see  Epithalamus 
Epithalamus,  467,  468,  505,  536 
Epithelium,  germinal,  17 

neuro-,  581,  586 
Epitrichium,  437 
Eponychium,  the,  440 
Epoophoron,  the,  415 
Equatorial  plate,  6 

Erganzungshole  (see  also  Completion  cavity),  55 
Erganzungsplatte  (see  also  Completion  plate), 

56,  59 

Erythroblasts,  270 
Erythrocytes,  270 
Eternod's  embryo,  136,  473 
Ethmoidal  labyrinth,  192 
Eustachian  tube,  590 
Evagination,  mesodermic,  73 
Exencephaly,  605 
Exoccipital  bone,  190 
Exoccelom,  92,  135, 
External  auditory  meatus,  origin  of,  143,  147 

ear,  first  appearance  of,  140 

form   of    the    body,    age    and    length    of 

embryos,  151 
development  of,  133 
extremities,  149 
branchial  arches,  face,  neck,  145 

geniculate  bodies,  see  Geniculate  bodies 

genital   organs    (see   also  Genital   organs, 
external),  423 


External,  genitalia,  first  appearance  of,  145 

influences    as    affecting    monsters,     612, 

613 

Extraembryonic  body  cavity,  92,  135 
Extraventricular  cell-divisions,  485 
Extrauterine  gestation,  115 
Extremities,  development  of,  149 

lower,  fused,  611 

malformations  of,  610,  611 

muscles  of  the,  303 

nerve  supply  of,  304 

one  or  more  abnormally  small  but  well 
formed,  6n 

one  or  more  defective,  6n 

one  or  more  wanting,  611 
Eye,  450,  457,  459,  460,  467,  506,  563 

anomalies  of,  591,  608 

anterior  chamber,  578 

ciliary  body,  577 

chorioid,  575 

cornea,  578 

first  indication  of  formation  of,  564 

formation  of  muscles  of,  302 

general  development  of,  563 

influence  on  nervous  system,  459 

innervation  of  muscles  of,  462 

iris,  577 

lens,  565 

muscles  of,  460 

optic  cup,  566,  569 
depression,  563 
nerve,  576 

retina,  570 

sclera,  575 

vitreous,  575 
Eyelashes,  578 
Eyelids,  578 

Fabricius  ab  Aquapendente,  XIII 
Face,  development  of,  145,  579 

malformation  of,  148,  608 
Facial  cleft,  oblique,  621 
Facialis,  VII,  nerve,  462,  464 
"Faecal  fistula,"  113 
Falx  cerebri,  542 
Fascia,  167 

dentata,  469,  548 
Fasciculi,  see  Tracts 
Fasciculus  cortico-spinal,  471 

cuneatus,  see  Columns  of  Burdach 

dorsal  spino-cerebellar,  471 

frontal  cortico-pontile,  471 

gracilis,  see  Columns  of  Goll 


INDEX 


629 


Fasciculus  mammillo-tegmental,  537 

medial  longitudinal,  466,  504,  511,  516 

occipital  cortico-pontile,  471 

retroflexus  of  Meynert,  538 

solitarius,  see  Tract  us  solitarius 

temporal  cortico-pontile,  471 

thalamomammillary,  537 

ventral  spino-cerebellar,  471 
Fat,  developing,  168 
Feet,  malformations  of,  611 
Female  pronucleus,  23,  33 
Femur,  204 
Fenestra  cochleae,  587 

vestibuli  (ovalis),  587 
Fertilization,  33 

factors  in  determining,  36 

of  human  ovum,  37 

references  for  further  study  of,  39 

significance  of,  38 
Fertilized  ovum,  33 

amphiaster  of,  33 

derivation  of,  XIV 
Fibers,  afferent  peripheral  nerve,  451 

afferent  root,  451,  490 

arcuate  (external),  515 
(internal),  508,  515 

association    (see    also   Cells,   association), 
556 

connective  tissue,  166 

cortico  pontile,  see  Cortico  pantile  fibers 

cortico-spinal,  see  Tracts,  pyramidal 

efferent  peripheral  nerve,  452,  486 
ventral  root  fibers,  486 

muscle,  294 

nerve,  various  views  concerning  develop- 
ment of,  493,  494 

neuroglia,  483 

olivo-cerebellar,  466,  521,  529 

projection    (ascending    and    descending), 
470,  546,  555,  559 

spiral  of  spermatozoon,  14 

visceral  (splanchnic),  487,  491 
Fibrillar  connective  tissue,  166 
Fibrillogenous  zone,  484 
Fibrils,  connective  tissue,  166 
Fibroblasts,  167 
Fibula,  204 
Filia  olfactoria,  502 
Fillet,  lateral,  466,  471,  523,  530 

medial,    466,    471,    520,    521,    530,    537, 

557 

Filum  terminate,  512 
Fimbria,  548 


Fimbriae,  414 

Fingers,  development  of,  150 
Fissure,  anterior  arcuate,  540 
calcarine,  554 
callosal,  551 
central,  554 
great  longitudinal,  542 
of  Rolando,  554 
of  Sylvius,  553 
pane  to-occipital,  554 
posterior  arcuate,  548 
prima,  of  His,  540 
primary,  of  cerebellum,  526 
secondary,  of  cerebellum,  526 
rhinal,  medial  and  external,  540 
ventral  longitudinal,  510 
Fissures  of  cerebral  hemispheres,  542 
Flechsig,    concerning    myelogenetic    areas    of 

pallium,  558,  559 
Flechsig's  tract,  471,  512 
Flemming,  concerning  amitosis,  4 
Flexure,  cephalic,  139 
cervical,  140 
dorsal,  139 
sacral,  140 
Flocculi,  526 

Floor  plate  (ventral  median  plate),  453 
Foetal  inclusion,  600 
membranes,  95 
allantois,  102 
amnion,  95 
chorion,  103 
earlier  stages  in   Mammals,  compared 

with  chick,  104 
function  of,  95 
in  Birds,  95 
in  Mammals,  103 
in  man,  in 
in  Reptiles,  95 

references  for  further  study  of,  132 
serosa,  103 
Foetus,  the,  145 
in  fcetu,  600 
papyraceus,  595 

Follicle,  Graafian,  rupture  of,  30 
Fontanelles,  194 
Foot,  development  of,  150 
Foramen  caecum  linguae,  321,  331 
of  Magendie,  513 
of  Monro,  531,  539,  542,  546 
of  Winslow,  378 
ovale,  234,  267 
transversarium,  185 


630 


INDEX 


Foramina  of  Luschka,  514 

Fore-brain  (prosencephalon) ,  454,  457,  467 

anterior  (cerebral)  commissure,  454 

chiasma  eminence,  454 

commissura  habenularis,  455 

corpora  striata,  455 

diencephalon,  467 

epiphysis  of,  454 

ganglia  habenulse,  455 

infundibulum,  454 

lamina  terminalis  of,  454 

pallium,  455 

paraphysis  of,  454 

pineal  body,  454 

processus  neuroporicus,  454  ' 

recessus  postopticus,  454 
praeopticus,  454 

rhinencephalon,  455,  467 

velum  transversum,  454 
Forel's  decussation,  517 
Formatio  reticularis,  465,  511,  515  to  518 

alba,  516 

grisea,  516 
Fornix,  anterior  pillars  (columns),  476,  537,  551 

body  of,  551 

commissure,  550 

longus,  552 

posterior  pillar  (columns)  548,  551 

psalterium,  550 

Forster,  concerning  malformations,  593 
Fossa  Sylvii,  539,  540,  552 
Frenulum  linguae,  328 
Fretum  Halleri,  231,  237 
Frog,  cleavage  in,  42,  43 
Frontal  bone,  194 

lobe,  542 
Froriep,  concerning  acustico-facialis  ganglion, 

S9i 

Funiculus,  dorsal  (posterior)  or  posterior  white 
column,  490,  503,  507 

lateral,  511 

teres,  524 

ventral  (anterior)  or  ventral  white  column, 
507 

ventro-lateral,  507 
Furcula,  the,  361 

Galea  capitis,  14,  21 
Gall  bladder,  346 
Ganglia,  cerebrospinal,  451 
sympathetic,  ciliary,  501 

otic,  501 

peripheral,  491 


Ganglia,  sympathetic,  prevertebral,  491 
sphenopalatine,  501 
submaxillary,  501 
vertebral,  491 
visceral,  459,  487 
Ganglion,  acoustic,  691 
acustico-facialis,  591 
cochlear,  499,  591 
Gasserian,  460,  500 
geniculate,  498,  591 
habenulae,  455,  533 
interpeduncular,  538 
nodosum,  495 
petrosum,  495 
Scarpa's   499,    (see   also   Nerves,    cranial, 

VIII) 

semilunar,  460,  500 
spinal,  490 
spirale,  499,  592 
vestibular,  499,  591 
Gartner,  canals  of,  416 

Gasserian  ganglion,  peripheral  branches  of,  460 
Gastral  mesoderm,  73 
Gastrointestinal  tract,  development  of  glands 

in,  343 

histogenesis  of  the,  342 
lymph  follicles  of,  344 
mucous  membrane  of,  342 
Gastroschisis,  313 
completa,  610 

Gastrothoracopagus  dipygus,  597 
Gastrula,  51 
Gastrulation,  in  Amphibians,  52 

yolk  content  in,  52 
in  Amphioxus,  51 

yolk  content  in,  51 
in  Birds,  57,  60  / 

yolk  content  in,  57 
in  hen's  egg,  60 
in  Mammals,  63 
in  man,  68,  85 
in  Reptiles,*  5  7 

yolk  content  in,  57 

in  water  salamander — Triton  taeniatus,  53 
Geniculate  bodies,  lateral  (external),  470,  471, 

505,  533,  555,  557,  57^ 
medial  (internal),  470,  471,  537,  555 
Geniculate  ganglion,  498 
Genital  cord,  419 
folds,  424 
glands,  the,  10 

changes  in  the  positions  of,  417 
development  of  the  ligaments  of,  417 


INDEX 


631 


Genital  glands,  differentiation  of,  405 
ducts  of,  413 
migration  of,  419 
stroma  of,  404 
organs,  external,  423 
first  appearance  of,  145 
(female),  clitoris,  424 
glans  clitoridis,  424 
labia  majora,  424 

minora,  424 
prepuce,  424 
vestibulum  vaginae,  424  ) 
(male)  penis,  424 
prepuce,  424 
raphe,  426 
scrotum,  426 
urethra,  424 
ridge,  389,  494,  423 
swellings,  424 
tubercle,  the,  424 
Gennari,  line  of,  557 
Genu  facialis,  517 
Germ  cells,  10 

female,  21 
male,  21 
disk,  45 
of  Birds,  45 
of  Reptiles,  60 
hill,  n,  410 
layers,  51 

diagram  showing,  54 
the  ectoderm,  51 
the  entoderm,  51 
the  epiblast,  51 
the  hypoblast,  51 
in  man,  85 
the  mesoderm,  68 
primary,  51 

German  method  of  measuring  embryos,  152 
Germinal  disk  (see  also  Germ  disk),  13 
epithelium,  404 
cells  of,  404 
rete  cords  of,  404 
sex  cords  of,  405 
spot,  12 

Giant  glomeruli,  399 
Gianuzzi,  crescents  of,  329 
Gill  arches,  musculature  of,  311,  459 
Gill-cleft  organs,  452 
Gills,  influence  on  nervous  system,  459 
Giraldes,  organ  of,  41 7 
Glands,  accessory  thyreoid,  332 
anterior  ligual,  328 


Glands,  Bartholin's,  403 

Brunner's,  343 

bulbo-urethral,  403 

carotid,  429 

coccygeal,  285 

Cowper's,  403 

duodenal,  343 

Ebner's,  322 

formation  of,  343 

genital,  10 

haemolymph,  282 

indifferent  (genital),  407 

lacrymal,  578 

lingual,  322 

liver,  345 

lymph,  280 

mammary,  442 

Meibomian,  578 

of  Mall,  578 

parotid,  328 

prehyoid,  332 

salivary,  327 

sebaceous,  442 

sublingual,  328 

submaxillary,  327 

sudoriferous,  442 

suprahyoid,  332 

suprarenal,  426 

sweat,  442 

thymus,  333 

thyreoid,  331 

uterine,  415 

vestibular,  403 
Glans  clitoridis,  424 

penis,  424 
Glia,  see  Neuroglia 
Glisson,  capsule  of,  346,  374 
Glomeruli  of  kidney,  393,  394 
Glomus  caroticum,  335,  429 

coccygeum,  285 
Glossopalatine  arch,  330 
Glossopharyngeus,  IX,  nerve,  462 
Goll,  column  of,  459,  471,  512,  518 

nuclei  of  columns  of,  459,  466,  467,  520 
Gonads,  10 
Graafian  follicle,  408,  409 

de  Graaf 's  description  of,  XIII 

primary,  407,  408 
Graf  v.  Spec's  ovum,  86 
Granules,  keratin,  439 
Gray  column    (dorsal  or  posterior),  458 
(ventral  or  anterior),  458,  507 

matter  of  cord  and  segmental  brain,  504 


632 


INDEX 


Gray  ramus  communicans,  492 

Ground  bundles  of  the  cord,  465,  504,  507,  509, 

5i6,  518 
Growth  of  bones,  176 

intracartilaginous,  176 

long,  176 

Gubernaculum  testis,  418,  419 
Gurwitsch,  concerning  peripheral  nerves,  493 

concerning  the  myelin  sheath,  494 
Gustatory  area,  558 

system,  452,  460 

Gyri,  transverse  of  temporal  lobe,  557 
Gyrus  ambiens,  541 

dentatus,  469,  548,  551 

olfactorius  lateralis,  541 

semilunaris,  541 

subcallosus,  552 

Habenula,  533 
Haemangiomata,  445 
Haemoblasts,  268 
Haemoglobin,  269,  270 
Haemolymph  glands,  282 
Haemopoiesis,  267 

views  concerning,  2 £7 
monophyletic,  267 
polyphyletic,  267 
Hair,  the,  440 

anomalies  of,  445 

cells,  586,  588,  589 

connective  tissue  follicle  cf,  440 

germs,  440 

Henley's  layer,  440 

Huxley's  layer,  440 

lanugo  the,  440 

papilla,  440 

shaft,  440 
Hamatate,  201 
Hammar,  concerning  the  tuberculum  impar, 

321 
Hands,  development  of,  150 

malformations  of,  611 
Haploid  number  of  chromosomes,  18,  22 
Hardesty,  concerning  development  of  neuro- 

glia,  479 

Hare-lip,  198,  212,  608,  609 
Harrison,  concerning  neurilemma  cells,  493 
Hartman,  concerning  cleavage,  49 
Harvey,  XIII 
Hassall's  corpuscles,  334 
Haversian  canals,  175 

lamellae,  175 

spaces,  175 


Head,  beginning  of,  138 
amniotic  fold,  96 
cap,  14 
fold,  79 
process  (primitive  intestinal  cord)  in  the 

chick,  62 
in  Mammals,  68 
skeleton,  186 

anlagen  of,  187,  189 

anomalies  of,  211 

bones  derived  from  the  branchial  arches, 

194 

cartilage  of,  187 

cartilaginous  primordial  carnium,  188 
chondrification  of,  187 
chondrocranium,  189 
diagram  of  skull  of  new-born  child,  193 
membrane    bones    of    the    skull,     192 
ossification  of  the  chondrocranium,  190 
periotic  capsule,  189 
table  showing  types  of  development  of 

bones  of,  198 

somatic  musculature  of  (eye,  tongue),  in- 
ner vation  of,  462 
Heart,  the,  227 

anomalies  of,  285,  595 
beat,  240 

changes  after  birth,  237 
development  of,  227 
double,  285 

first  indications  of,  139 
interventricular  furrow,  231 
migration  of,  372,  375 
muscle,  histogenesis  of,  311 
origin  of,  227 
papillary  muscles  of,  237 
septa  of,  233 
sinus  venosus,  222,  232 
valves,  236 
Heidenhain,  9 
Held,  concerning  early  development  of  neuro- 

fibrils,  484 
Helix,  591 

Hemicrania,  604,  605 
Hemispheres,    cerebral,    457,    470,    474,    538, 

541  to  560 
of  cerebellum,  526 
Henle's  layers,  440 

loop,  394 

Hensen,    concerning    peripheral    nerves,    494 
Hensen's  cells,  588 

node,  61,  66,  87 
Hepatic  cords,  349 


INDEX 


633 


Hepatoduodenal  ligament,  380 

Hepatogastric  ligament,  380 

Heredity,  important  factor  in  teratogenesis,  612 

in    relation    to    anomalies    of    muscular 
system,  314,  315 

influence  of,  in  albinism,  445 
Hermaphroditism,  434 

bilateral,  434 

false,  434 

feminine  false,  434 

lateral,  434 

masculine  false,  434 

true,  434 

unilateral,  434 
Hernia,  diaphragmatic,  382 

umbilical,  113 
Herrick,  concerning  the  gustatory  tracts,  468 

concerning  gustatory  pathway,  519 
Hertwig,    concerning   duplicity   from   double 
gastrulae,  600 

concerning  fertilization,  38 

concerning  the  formation  of  the  primitive 
streak,  61 

concerning  the  mammary  gland,  443 

concerning  mesoderm  formation  in  Triton 
and  Amphioxus,  73 

concerning  spina  bifida,  607 

on  production  of  monsters,  614 
Heteromeric  column  cells,  503 
Hind-brain  (metencephalon),  455 
Hippocampal  fissure,  548 

formation,  469,  543,  548,  552 
Hippocampus  major,  548,  552 
His,  concerning  age  and  length  of  embryos,  151 

concerning  angulus  praethalamicus,  540 

concerning  germinal  cells,  479 

concerning  limbus  corticalis  and  medul- 
laris,  542 

concerning  neuroblasts,  485 

concerning  olfactory  nerve,  581 

concerning  peripheral  nerves,  494 

cylinder  furrow  of,  509 

marginal  furrow  of,  509 

trapezoid  area  of,  541 

Hochstetter,  concerning  the  bucco-nasal  mem- 
brane, 579,  580 
Holorachischisis,  605 
Horns,  anterior   (ventral  gray  column),  458, 

507 

Horseshoe  kidney,  429 
Howslip's  lacunae,  172 
Huber,  concerning  cleavage,  50 
Humerus,  200 


Hunteri,  gubernaculum,  419 
Huxley's  layer,  440 
Hyaloid  canal,  576 

membrane  of  vitreous,  575 
Hyaloplasm,  i 
Hydatid  of  Morgagni,  417 

non-stalked,  414 
Hydramnios,  112 
Hydrencephalocele,  605 
Hydrencephaly,  605 
Hydrocephaly,  congenital,  605 
Hydromeningocele,  605 
Hydromicrencephaly,  605 
Hymen,  the,  415 

anomalies  of,  434 
Hyoid,  197 

arch,  464 

Hyperkeratosis,  444 
Hypermastia,  445 
Hyperthelia,  445 
Hypertrichosis,  445 
Hypoblast  (see  also  Entoderm),  51 

formation  of,  51 
Hypochordal  bar,  184 
Hypoglossus,  XII,  nerve,  462,  515 
Hypophyseal  pouch,  531 
Hypophysis,  467,  533 
Hypospadias,  432 

Hypothalamic  region,  see  Hypothalamus 
Hypothalamus,  467,  468,  478,  53 1,  53^ 
Hypotrichosis,  445 

Ichthyosis,  444 

Identity  of  chromosomes,  7,  26 

Bium,  the,  203 

Imperforate  hymen,  434 

Incisive  bone,  195 

Incisura  prima,  540 

Incus,  197,  589 

Indifferent  glands,  407 

anomalies  derived  from,  434 

stage,  diagram  showing,  423 

table  showing  structures  derived  from, 

423 

structures,  404 
Indusium  griseum,  551 
Infracardiac  ramus,  366 
Infundibular  process,  532 
Infundibulum,  454,  478,  531 
Inguinal  ligament,  418 

ring,  the,  420 
Iniencephaly,  605 
Inner  cell  mass,  48,  133 


634 


INDEX 


Inner  cell  mass,  layer   of   neural   tube,   485, 

502,  514,  527,  530,  542,  554 
Innominate  artery,  243 

bone,  203 

veins,  254 

Insula  (island  of  Reil),  552 
Integumentary  system,  the,  437 

anomalies  of,  444 

glands  of  the  skin,  442 

hair,  440 

nails,  439 

skin,  437 

Inter-brain  (diencephalon),  see  Diencephalon 
Intercarotid  ganglion,  429 
Intercellular  substance,  origin  of,  165 
Intermediary  plexus  of  lymph  glands,  281 
Intermediate  areas  of  Flechsig,  558 

cell  mass,  80 

(medullary)  layer  of  telencephalon,  542 

plate,  509,  511 

Intermuscular  connective  tissue,  310 
Internal  capsule  of  fore-brain,  472,  537,  545, 
546,  558 

geniculate  bodies,  see  Geniculate  bodies 
Interrenal  organs,  428 
Interventricular  furrow,  231 
Intervertebral  fibrocartilage,  180,  184 
Intervillous  spaces,  127 
Intestinal  crypts  of  Lieberkiihn,  343 

region,  317 

tract,  colon,  338,  340 
duodenum,  338 

mesenterial  small  intestine,  338 
vermiform  appendix,  341 

umbilicus,  101 
Intestine,  the,  337 

anomalies  of,  357 

crypts  of  Lieberkiihn,  343 

loops  of,  338,  339 

villi  of,  343 
Iris,  577 

defective  pigmentation  of,  445  ] 
Ischiopagus,  596 

parasiticus,  597 
Ischiothoracopagus,  597 
Ischium,  the,  203 
Island  of  Reil,  552 
Islands  of  Langerhans,  354 
Isthmus,  455,  513 
Iter,  see  Aquceductus  Sylvii 

Jacobson's  organ,  581 
Janus  asymmetros,  598 


Janns,  symmetros,  598 

Jaws,  malformations  of,  608,  609 

splanchnic    musculature,    innervation   of, 

462,  464 

Johnston,  concerning  mesencephalic  root  of  V, 
523 

concerning  the  optic  recess,  531 
Joint  capsule,  207 

cavity,  207 
Joints,  205 

diarthrosis,  207 

synarthrosis,  206 

synchondrosis,  206 

syndesmosis,  206 
Jugular  lymph  sac,  275,  278 

Kallius,  concerning  the  mammary  gland,  442 

Karyolysis,  270 

Karyoplasm,  i 

Karyorrhexis,  270 

Karyosomes,  i 

Keibel,    concerning    origin    of    endolymphatic 

appendage  in  the  chick,  583 
Keratin  granules,  439 
Kidney,  the,  391 

anomalies  of,  426 

Bowman's  capsule,  395 

capsule  of,  398 

changes  in  position  of,  399 

columns  of  Bertini,  397 

congenital  cysts  of,  430 

convoluted  tubule,  Henle's  loop  of,  394 

cortex  of,  398 

derivation  of,  391 

floating,  430 

glomeruli  of,  393 

and  blood  vessels  of,  394 
hilus  of,  397 

Malpighian  pyramids  of,  397 
medulla  of,  398 
metanephric  blastema  of,  392 
migration  of,  399 
movable,  430 
nephrogenic  tissue  of,  392 
relation  to  suprarenal  gland,  428 
renal  columns  of,  397 
corpuscle  of,  397 
papillae  of,  393,  398 
pelvis,  391 
pyramids  of,  397 
tubules  of,  convoluted,  393 

straight,  392 
ureter,  391 


INDEX 


635 


Kidney,  urinary  function  of,  399 

Knomer,    H.    McE.,    on    production    of 

monsters  in  single  embryos,  614 
Kolliker,  XIV 

concerning  formation  of  incisive  bone,  196 

Krause,   concerning   origin   of   endolymphatic 

appendage   in   chick   and   Amphibia, 

583 
Kupffer,  v.,  concerning  the  acoustic  ganglion, 

588 

concerning  the  differentiation  of  the  neu- 
ral tube,  453 
concerning  olfactory  placodes,  579 

Labia  majora,  424 

minora,  424 
Lacrymal  bone,  194 

duct,  579 

glands,  578 
Lacunae,  171 
Laloo,  597 
Lamellae,  Haversian,  175 

interstitial,  175 
Lamina  affixa,  550 

cribrosa  (of  eye),  577 
(of  nose),  192 

infrachorioidea,  547,  548 

lateral  pterygoid,  194 

medial  pterygoid,  193 

perpendicularis,  192 

terminalis,  454,  539,  547 
Langerhans,  islands  of,  354 
Langhan's  layer,  121 

outgrowths  from,  122 
Lanugo,  the,  440 
Laryngeal  pouch,  361,  368 
Larynx,  the,  361 

anomalies  of,  368 

cartilages  of,  362 

development  of,  197,  361 
Lateral  geniculate  bodies,  see  Geniculate  bodies 

lemniscus,  466 

line  cranial  nerves,  462 
organs,  451,  452,  460,  462 

nasal  process,  148 

plate  (of  mesoderm),  71 

plates  (of  neural  tube),  453 

recesses  of  fourth  ventricle,  513 
Leg,  development  of,  150 
Lemmocytes,  492 
Lemniscus,  lateral,  see  Fillet,  lateral 

medial,  see  Fillet,  medial 
Lens,  565 


Lens,  anterior  epithelium  of,  567 

area,  565 

capsule,  569 

fibers  of,  567 

hyaloid  artery  of,  569 

in  vagina  tion,  565 

membrana  pupillaris  of,  569 

tunica  vasculosa  of,  569 

vesicle,  565 

Leopold,     concerning     ovulation     and     men- 
struation, 30 

ovum  of,  85 
Leucocytes,  270 

Lewis,  concerning  anomalies  of  pancreas,  358 
Lieberkiihn,  crypts  of,  343 
Life  cycle,  complete,  in  the  female,  410 

complete,  in  the  male,  412 
Ligaments,  broad,  of  the  uterus,  422 

costo- vertebral,  184 

diaphragmatic  of  the  mesonephros,  418 

hepatoduodenal,  380 

hepatogastric,  380 

inguinal,  418 

middle  umbilical,  115,  401 

origin  of  fibers  of,  167 

ovarian,  422 

round,  of  liver,  261 
of  uterus,  422 

sphenomandibulor,  196 

stylohyoid,  197 

suspensory  of  the  lens,  578 

umbilical,  248 
Ligamentum  arteriosum,  240,  243,  267 

coronarium  hepatis,  376 

suspensorium  (falciforme)  hepatis,  376 

teres  hepatis,  376 
Limb  bud,  lower,  141,  149,  306 

upper,  141,  149,  304 
Limb  buds,  differentiation  of,  304,  306 
Limbus  corticalis  of  His,  542 

fossae  ovalis,  236 

medullaris,  542 
Lingual  glands,  322 

papillae,  321 

tonsils,  330 
Lingula  (of  cerebellum),  526 

(of  sphenoid),  191 
Linin,  i 
Lip,  clefts  of,  196,  212,  608,  609 

lower,  origin  of,  144 

upper,  origin  of,  144 
Liquor  amnii,  98 

folliculi,  409 


636 


INDEX 


Liver,  the,  345 

anomalies  of,  357 

bile  capillary  of,  349 

capsule  of  Glisson,  346 

cells  of,  349 

circulation  of,  346 

ducts  of,  346 

gall  bladder  of,  346 

growth  of,  349 

hepatic  cylinders  of,  347 

histogenesis  of,  349 

lobe  of  Spigelius,  349 

lobes  of,  348 

pars  hepatica  of,  345 

cystica  of,  345 
round  ligament  of,  261,  349 
vasa  aberrantia  of,  350 
veins  of,  260,  348 
Lobus  pyriformis,  469,  541 
Loeb,  concerning  production  of  monsters,  614 
Longitudinal  fasciculus,  medial,  466 
Lordosis,  604 
Lower  extremities,  203 
Lumbar  enlargement,  459 
Lunate  bone,  200 
Lung  groove,  360 
Lungs,  the,  364 

anomalies  of,  368 
atria  of,  365 
changes  in,  at  birth,  367 
ducts  of,  365 

eparterial  bronchial  ramus  of,  365,  368 
influence  on  nervous  system,  459 
lobes  of,  365 
weight  of,  367 
Lunula,  the,  440 
Luschka,  foramina  of,  514 
Lutein  cells,  or  granules,  31 
Lymph,  origin  of,  283 
follicles,  284 

of  gastrointestinal  tract,  344 
of  tonsils,  330 
glands,  the,  280,  345 
hearts,  274,  275,  278 
sacs,  274,  275,  278 
Lymphangiomata,  445 
Lymphatic  system,  the  273 
glands  of,  280 
glomus  coccygeum,  285 
haemophoric  function  of,  279 
spleen,  283 
thymus  gland,  285 
views  concerning,  273 


Lymphocytes,  270 

primitive,  268,  269 

Macromeres,  47 
Macrostomus,  609 
Macula  acustica,  589 

lutea,  572 

Magendie,  foramen  of,  513 
Magma-re  ticulare,  155 
Male  pronucleus,  23,  33 
Malformation   involving   one  individual    (see 

Monsters),  604 
Malformations  of  more  than  one  individual  (see 

Duplicate  monsters),  593 
Mall,  concerning  development  of    the  maxilla, 

195 

concerning  development  of  pyramids,  555 
concerning  ossification  of  incisive  bone,  195 
formulae  for  estimating  age  of  embryos,  153 
on  faulty  implantation  of  the  ovum,  613 
on  theories  of  production  of  monsters,  612 
Malleus,  197,  589 
Malpighian  corpuscle,  387 

pyramids,  397 
Mammary  gland,  the,  442 
anomalies  of,  445 
areolar  glands  of,  443 
colostrum  corpuscles,  444 
growth  of,  in  female,  443 
growth  of,  in  male,  443 
nipple,  443 
of  pregnancy,  443 
Mammillary  bodies,  533 

region,  478,  533 
Mandible,  196 

Mandibular  process,  140,  147,  318 
Mantle  fibers,  6 

layer  of  neural  tube,  485,  502,  514,  527, 

530,  542,  554 
Manubrium  sterni,  186 

Marchand's    fusion    theory    of    symmetrical 
duplicity,  599 

scheme  of  duplicate  monsters,  593 
Marginal  furrow  of  His,  509 

layer  of  neural  tube,  479,  514,  527,  530,  542 
Mark  and  Long,  concerning  maturation,  22 
Marrow,  177 

cavity,  primary,  173 

formation  of  blood  cells  in,  271 

red,  178 

spaces,  primary,  171 

yellow,  178 
Marsupials,  early  nutritional  conditions  in,  108 


INDEX 


637 


Masculine  false  hermaphroditism,  434 
Massa  intermedia,  535 
Mastoid  process,  191 
Maternal  impressions,  612 
Maturation,  17 

and  mitosis,  significance  of,  25 

in  Ascaris,  17 

of  the  ovum,  21 

of  the  sperm,  17 

references  for  further  study  of,  32 
Maxilla  bone,  194 
Maxillary  process,  140,  147,  318 
McMurrich,     concerning    derivation    of    the 
dermis,  438 

concerning  umbilical  cord,  129 
Mechanical  theory  of  monsters,  613 
Meckel's  cartilage,  189,  194,  196 

diverticulum,  113,  339 
Medial  fillet,  see  Fillet,  medial 

geniculate  bodies,  see  Geniculate  bodies 

lemniscus,  see  Fillet,  medial 

longitudinal  fasciculus,  466,  504,  511,  516, 

5i7 

nasal  process,  148 
Mediastinum  testis,  413 
Medulla  oblongata,  477,  512 

taenia  of,  513 
Medullary  cords,  406,  407 

folds,  in  chick  blastoderm,  63 

groove,  67 

layer  of  telencephalon,  542,  554 

sheath,  see  Myelin  sheath 
Megakaryocytes,  273 
Megaloblasts,  272 
Meibomian  glands,  578 
Meiolecithal  ova,  12 
Meissner,  plexus  of,  491 

tactile  corpuscles  of,  438 
Membrana  preformativa,  325 

tectoria,  588 

undulatoria,  15 

Membrane  bones  of  the  skull,  192 
Mendel's  law  of  segregation,  26 
Meningocele,  605 
Meningoencephalocele,  605 
Menstruation,  29 

relation  to  fertilization,  29 

relation  to  ovulation,  29 
Merocytes,  59 
Merorachischisis,  606 
Mesencephalon  (mid-brain),  84,  454,  475 
Mesenchyme,  165 
Mesenterial  small  intestine,  338 


Mesenteries,  370,  377,  380 

anomalies  of,  382 
Mesentery  of  the  jejunum,  380 
Mesoappendix,  381 
Mesocardium,  dorsal,  227,  372 

ventral,  227,  372 
Mesocolon,  ascending,  381 
descending,  381 
sigmoid,  381 
transverse,  380 

Mesoderm,  derivatives  from,  161 
development  of,  134 
extraembryonic,  88 

origin  of,  90 

formation  in  Amphibians,  72 
in  Amphioxus,  68 
in  Birds,  75 
in  the  frog,  73 
in  Mammals,  81 
in  man,  86,  88,  91, 92 
in  Reptiles,  74 
gastral,  73 
intraembryonic,  88 

origin  of,  91 

layers  of,  in  von  Spec's  embryo,  88 
parietal,  71,  134 
peripheral,  83 
origin  of,  91 
peristomal,  54,  73 
splanchnic,  102,  342 
visceral,  71,  83,  134 
Mesodermic  evagination,  73 

somites,  68,  139,  293,  300 
Mesoduodenum,  380 
Mesogastrium,  dorsal,  335,  377 

ventral,  336,  377 
Mesolecithal  ova,  1 2 
Mesonephric  duct,  386 
mesentery,  418 
ridge,  385,  388 
Mesonephroi,  atrophy  of,  in  the  female,  415 

in  the  male,  416 
Mesonephros,  386 

Bowman's  capsule,  387 
degeneration  of,  390 
diaphragmatic  ligament  of,  389,  418 
disappearance  of,  390 
function  of,  389 
glomerulus  of,  387 
Malpighian  corpuscle  of,  387 
renal  portal  system  of,  390 
significance  of,  390 
tubules  of,  386 


638 


INDEX 


Mesorchium,  406,  419 

Mesorectum,  381 

Mesosalpinx,  416,  422 

Mesothelium,  370,  423 

Mesovarium,  406,  419,  422 

Metacarpals,  201 

Metanephric  blastema,  392 

Metanephros,  see  Kidney 

Metaphase,  6 

Metaplasm,  i,  2 

Metaplexus,  513 

Metapore,  513 

Metatarsals,  205 

Metathalamic  portion  of  thalamus,  536,  546 

Metathalamus,    see    Metathalamic    portion    of 

thalamus 
Metazoa,  10 

Metencephalon  (hind-brain),  84,  455 
Method  of  measuring  embryos,  American,  153 

German,  152 
Metopic  suture,  194,  212 
Metopism,  212 
Meyer,  concerning  mesencephalic  root  of  V,  5  23 

Adolf,  concerning  segments  of  segmental 

brain  and  cord,  505,  506 
concerning  suprasegmental  and  segmen- 
tal structures,  450,  457 
Meynert,  solitary  cells  of,  558 
Meynert's  decussation,  530 
Micrencephaly,  605 
Microbrachius,  611 
Microcephaly,  605 
Micrognathus,  356,  609 
Micrognathy,  356,  609 
Micromelus,  611 
Micromeres,  47 
Microphthalmia,  591,  608 
Micropus,  611 
Micropyle,  36 
Microstomus,  609 
Mid-body,  8 
Mid-brain  (mesencephalon),  454,  475 

optic  lobes,  455 

roof,  457,  467 

descending  tracts  to  after-brain  and  cord 

segments,  467 
Middle  peduncle  of  cerebellum,  466,  471,  473, 

523,  530 

Milk  ridge,  the,  442 
teeth,  323,  326 

Mimetic  musculature  and  its  innervation,  464 
Minot,  concerning  foetal  membranes  of  um- 
bilical cord,  129 


Mitoses  (see  also  Cell  proliferation  and  Gemi- 
nal  cells],  479,  514,  519,  536 

extraventricular,  485 

of  neural  tube  cells,  479,  530 
Mitosis,  4 

and  maturation,  significance  of,  25 

diagrams  of  successive  stages  of,  5,  7 

of  mucous  cells  of  stomach,  344 

multipolar,  9 

phases  of,  4 

pluripolar,  9 
Mitotic  division  of  sex  cells,  404 

figure,  6 

Mitral  cells,  505 
Monaster,  6 
Monobrachius,  6n 
Monochorionic  quadruplets,  599 

triplets,  599 

twins  (equal),  594,  595 

(unequal),  595 

Mononuclear  leucocytes,  270 
Monopolar  cells,  485 
Monopus,  611 
Monotremes,  early  nutritional  conditions  in, 

1 08 

Monro,  foramen  of,  531,  539,  542,  546 
Monsters,  amniotic  adhesions,  611 

causes  underlying  origin  of,  612 

defects  in  region  of  face  and  neck,  and 
their  origin,  609 

defects  in  region  of  neural  tube,  604 
origin  of,  607 

defects   in    the   thoracic   and    abdominal 

regions,  and  their  origin,  610 
in  single  embryos,  614 

malformations  of  extremities,  610 
polysomatous,  613 

production  of  duplicate,  613 
Montgomery,  concerning  areolar  glands,  443 
Morgagni,  hydatid  of,  417 

concerning   development   of   blastomeres, 
610 

concerning  production  of  spina  bifida,  614 

liquor,  567 

non-stalked  hydatid  of.  414 
Morula,  40,  46,  48,  133 
Mossy  fibers,  530 
Motor  cortex  (see  also  Pallittm,  torecentral  area 

of],  558 
Mouth,  the,  317 

angle  of  the,  141, 148,  318 

anomalies  of,  356 

development  of,  319 


INDEX 


639 


Mouth,  influence  on  nervous  system,  459 
origin  of,  317 
slit,  148 

Mucous  tissue,  129 
Mullerian  ducts,  399,  413 

atrophy  of,  417 
Multiple  placentae,  no 
Multiplicity,  597 
Muscle  fibers,  change  of  direction  of,  295 

theories  concerning  internal  structure  of, 

308 

heart,  histogenesis  of,  311 
plates,  164,  294 

formation  from  primitive  segment,  71 
tissue,    histogenesis    of    striated     volun- 
tary, 307 
smooth,  311 

Muscles,  branchiomeric,  302 
differentiation  of,  305 
extrinsic,  of  the  upper  extremity, 
anomalies  of,  314 
lattissimus  dorsi,  305 
levator  scapulae,  305 
pectoralis,  305 
serratus,  305 
trapezius,  305 
innervation  of,  294 
of  the  extremities,  303 
derivation  of,  303 
derivation   from   premuscle    sheath   of 

muscles  of  lower  extremity,  306 
differentiation  from    mesenchymal  tis- 
sue, 304 

extrinsic  muscles,  305 
migration  of,  306 
of  the  head,  300 
chondroglossus,  303 

constrictor  muscles  of  the  pharynx,  303 
development  and  innervation  of,  302 
digastricus,  302,  303 
epicranius,  303 
glossopalatinus,  303 
laryngeal,  303 
masseter,  302 
mentalis,  303 

muscles  of  the  soft  palate,  303 
mylohyoideus,  302 
obliquus  inferior,  302 

superior,  302 
platysma,  303 

quadratus  labii  superioris,  303 
recti  inferior,  302 
medialis,  302 


Muscles  of  the  head,  recti  superior,  302 
rectus  lateralis,  302 
pterygoidei,  302 
risorius,  303 
stapedius,  303 
sternomastoideus,  303 
stylohyoideus,  303 
stylo-pharyngeus,  303 
temporalis,  302 
tensor  tympani,  302 
veil  palatini,  302 
trapezius,  303 
triangularis,  303 
of  the  trunk,  295 
coccygeus,  300 
geniohyoideus,  299 
intercostales,  298 
levator  ani,  300 
longus  capitis,  298 
longus  colli,  298 
olbiqui  abdominis,  298 
omohyoideus,  299 
perineal,  300 
psoas,  298 
pyramidalis,  299 
quadratus  lumborum,  298 
rectus  abdominis,  299 
capitis  anterior,  298 
sacrospinal,  300 
scaleni,  298 

sphincter  ani  externus,  300 
sternohyoideus,  299 
sternothyreoideus,  299 
transversus  abdominis,  298 

thoracis,  298 

Muscular  system,  the,  293 
amomalies  of,  313 
skeletal  musculature,  293 
visceral  musculature,  293,  311 
Musculature,  hyoid,  302 
skeletal,  293 

diaphragm,  the,  300 
early  character  of,  293 
loss  of  segmental  character,  294,  295 
muscles  of  the  extremities,  303 
of  the  head,  300 
of  the  trunk,  295 
myotomic  origin,  293,  300,  303 
visceral,  311 

mesodermic  origin  of,  311 
Myelencephalon  (after-brain),  84,  455,  512 
Myelin  sheath,  478,  494 
Myeloblasts,  177,  272 


640 


INDEX 


Myelocystocele,  606 

Myelocytes,  177,  272 

Myelogenetic     fields      (areas)      of     Flechsig, 

558 

Myelomeningocele,  606 
Myeloplaxes,  177,  272 
Myelospongium,  479,  483 
Myoblasts,  303,  307 
Myocardium,  228,  311 
Myoccel  (coelom),  71,  370 
Myotomes,  163,  294 

alternation     of,     with      vertebrae,      180, 

295 

change  of  direction  in  fibers  of,  295 
degeneration  of,  295 
differentiation  of,  295 
fusion  of,  295,  314 
longitudinal  splitting  of,  295,  314 
migration  of,  295,  314 
tangential  splitting  of,  295,  314 

Naevi  pigmentosi,  445 
Nail  groove,  439 

wall,  439 
Nails,  the,  439 

epitrichium  of,  440 

eponychium  of,  440 

lunula  of,  440 

migration  of,  439 

replacement  of,  440 
Nanocephaly,  605 
Nares,  outer,  580 

posterior,  580 
Nasal  bone,  194 

conchae,  580 

fossae,  140,  589 

pit,  148,  319,  589 

process,  lateral,  148 
medial,  148 

sacs,  589 

septum,  192,  319 
Naso-f rental  process,  147,  317 
Naso-optic  furrow,  142,  147,  579 
Navicular  bone,  200 
Neck,  development  of,  145 
Neck-rump  length  of  embryos,  153 
Neopallial  commissure   (see  also  Corpus  cal- 

losum),  468 
Neopallium,  467,  468,  472,  552  to  560 

centrifugal  connection  (see  also  Tracts, 
pyramidal,  Cortico-pontile  fibers  and 
Fibers,  projection  descending),  471, 472, 
546,  555,  558 


Neopallium,  centripetal  connections   (see  also 
Fillets,  Thalamic  radiations  and  Fibers, 
projection  ascending),  470,  471,   537, 
546,  555,  558 
Nephrogenic  tissue,  392 
Nephrostomes,  386 
Nephrotomes,  388 
Nerve  fibers,  afferent  peripheral,  451,  486 

efferent  peripheral,  452 
Nerves,  cranial,  abducens,  VI,  462,  515 

nucleus  and  roots  of,  488,  515,  517,  524 
acoustic  (auditory)  VIII,  462,    465,  499, 

Soo,  503,  518,  588 
cochlear  ganglion,  499,  588 

part,  462,  465 
cochlear  root,  500,  588 
vestibular  ganglion,  499,  588 

part,  462,  465 

vestibular  root,  500,  503,  518,  588 
facialis,  VII,  462,  464 

afferent  roots,  solitary  tract,  499,  518 
chorda  tympani,  498 
efferent  nucleus  and  roots  of,  488,  517 
geniculate  ganglion  of,  498,  588 
glossopharyngeus,  IX,  462,  464 
afferent  part  of,  462 

roots,  499 

efferent  nucleus  and  efferent  root  of,  488 
ganglion  of  the  trunk  (petrosum),  495 

of  the  root,  495 

lingual  and  tympanic  branches  of,  498 
great  superficial  petrosal  branch,  498 
hypoglossus,  XII,  462,  515 

nucleus  and  roots  of,  468,  524 
lateral  line,  462 
olfactory,  I,  467,  501,  505 

terminal  nuclei,  or  mitral  cells  of  the 

olfactory  bulb,  505 
optic,  II,  454,  467,  505,  530,  576 

ganglion  cells  of,  505 
oculomotor,  III,  462 

nucleus  and  roots  of,  488 
somatic,  462  to  466 
spinal  accessory,  XI,  464,  495 
efferent  fibers  of,  496 

nuclei  and  roots  of,  488 
splanchnic,  460  to  465 
trigeminus,  V,  460,  462,  464 

afferent  root  (portion  major),  and  spinal, 

V,  460,  501,  503,  518 
efferent  nuclei  and  roots  of,  488 
Gasserian  or  semilunar  ganglion,  460, 
500 


INDEX 


641 


Nerves,  trigeminus,  mandibular  branch,  500 
maxillary  branch,  500 
mesencephalic  root  of,  523 
opthalmic  branch,  500 
trochlear,  IV,  462 

nucleus  and  roots  of,  488 
vagus,  X,  462,  464 
afferent  roots,  499 
efferent  fibers  of,  496 

nuclei  and  roots  of,  488,  518 
ganglia  of  root,  495 
ganglion  of  trunk  (nodosum),  495 
Nerves,  spinal,  peripheral,  dorsal  branch  of,  487, 

490 

ventral  branch,  487,  490 
Nervous  system,  the  447 
anomalies  of,  560 
anterior  neuropore,  451 
brain,  453 
central   distinguished   from   peripheral, 

449 

cerebrospinal  ganglia,  45 1 
components  of ,  afferent  and  efferent,  447 
derivation  of,  451 
epichordal  segmental  brain  and  nerves, 

459 

general  considerations  of,  447,  448 
human,  489 
nerve  fibers,  451 
neural  crest,  451 

folds,  451 

groove,  451 

plate,  451 

tube,  451 

primitive  nervous  mechanism,  448 
root  fibers  of,  451 
spinal  cord  and  nerves,  453,  457 
three-neurone  reflex  arc,  450 
two-neurone  reflex  arc,  448 
vertebrate,  450 
central,  449 

supraseg mental  structures  of,  450,  457 
human,    afferent     peripheral    and     sym-« 

pathetic  neurones,  489 
anomalies  of,  560 
cell  proliferation  of,  479 
cerebellum,  455,  457,  466,  512,  525 
corpora  quadrigemina,  467,  517,  530 
development    of    the    lower    (interseg- 

mental)  intermediate  neurones,  502 
differentiation  of  peripheral  neurones  of 

cord  and  epichordal    segmental  brain, 

486 


Nervous  system,  human,  early  differentiation 

of  nerve  elements,  483 
epicordal  segmental  brain,  512 
epithelial  stage  of,  479 
further  differentiation  of  neural  tube, 

506 
general    development    of,    during    first 

month,  472 
histogenesis  of,  478 
spinal  cord,  506 
peripheral,  447 
effectors  of,  448 
receptors  of,  448 
sympathetic,  458 

efferent  peripheral  visceral  neurones  of, 

45i 

vertebrate,  bilateral  character  of,  450 
cephalization,  450 
general  features  compared  with  human, 

457 

general  plan  of,  450 

segmentation  of,  450 

typical,  450 
Net  knots,  i 
Neural  crest,  75,  451,  490 

relation  to  cerebrospinal  ganglia,  451 

segmentation  of,  451 

separation  of,  451 
folds,  69,  451,  472 

fusion  of,  451,  472 

groove,  69,  73,  74,  80,  85,  87,  135,  451,  472 
plate,  77,  451,  472 

differentiation  of,  453 
tube,  70,  80,  451,  472 

alar  plate,  477,  512,  515,  519 

basal  plate,  477,  512,  514 

blood  vessels  of,  508 

cells  of,  479,  481,  483,  484 

cervical  flexure,  478 

defects  in  the  region  of,  607 

floor  plate  of,  453,  473 

further  differentiation  of,  506 

lateral  plates  of,  453,  473 

layers  of,  479,  485,  514 

limiting  membranes  of,  479 

neuromeres,  456,  477 

order  of  development  of,  478,  506,  515, 

5i9,  542 

origin  of  malformations  of,  607 

roof  plate  of,  453,  473,  513 

sulcus  limitans,  477,  512 
Neurenteric  canal,  70,  317 
Neurilemma,  478,  492 


642 


INDEX 


Neurilemma,  cells  of,  492 
Neuroblasts  of  His,  485 
Neuro-epithelium,  581,  586 
Neurofibrils,  478,  484,  489 
Neuroglia  cells,  481,  485 

fibers,  483 

Neuromeres,  456,  477 
Neurone  layer,  see  Mantle  layer 
Neurones,  afferent  peripheral,  447,  457,  489  to 
502 

afferent  versus  efferent,  457 

association,  457,  468,  528,  530,  558 

central,  449 

differentiation  of,  478 

distal  (first)  optic,  576 

efferent  peripheral,  447,  457,  486  to  489 

intermediate,  449,  459,  502 

intersegmental    (see  also  Ground  bun- 
dles and   Formatio   reticularis) ,    459, 
465,  478,  502,  to  506,  515 
of  epichordal  segmental  brain,  465 
to  suprasegmental  structures,  459 

intersegmental,  of  epichordal  brain,  515 
to  518 

middle  (second)  optic,  576 

somatic  efferent,  459 

splanchnic  efferent,  459 

suprasegmental,  478 
Neuropore,  70 

anterior,  451,  473 
Nipple,  the,  443 
Nodule  of  cerebellum,  526 
Normal  embryos,  154 
Normoblasts,  270 
Nose,  450,  457,  505,  582 

anomalies  of,  212,  608 

bucco-nasal  membrane,  580 

Jacobson's  organ,  581 

nasal  conchae,  580 

origin  of,  144,  579 

primitive  choanen,  580 
palate,  580 

sinuses  of,  580 
Notochord,  68,  178 
Nuck,  diverticulum  of,  422 
Nuclear  groups,  1 23 

layer  of  neural  tube,  479 

membrane  of  typical  cell,  i 

reticulum  of  typical  cell,  i 
Nuclei,  lateral,  466 

of  columns  of  Burdach,  459,  466,  471,  520 

of  columns  of  Goll,  459,  466,  471,  520 

of  thalamus,  537 


Nuclei,  pontile,  466,  519,  530 

receptive,  467 

red  (ruber),  466,  517 

terminal  of  afferent  nerves  of  epichordal 

brain,  518  to  525 
of  tractus  solitarius,  462,  519,  ^24 
of  V,  460,  520,  523,  524 
of  VIII,  462,  522 

tracts  from  Deiter's,  466,  511 
Nucleoli,  function  of,  2 

false,  i 

true,  2 

Nucleoplasm,  i 
Nucleus,  the,  i 

ambiguous,  X,  488,  517 

caudatus  of  corpus  striatum,  546 

commissuralis,  519 

dentatus,  471,  472,  530 

diffuse,  2 

dorsal  efferent,  X,  488 

functions  of,  2 

habenulae,  455,  533 

incertus,  524 

inferior  olivary,  466,  519,  520,  524 

intercalatus,  524 

lateral,  520 

lenticularis,  546 

lentiformis,  546 

of  Darkschewitsch,  517 

structure  of,  i 
Nutrition  of  earliest  stages  of  embryo,  104 

Obex,  513 

Obturator  foramen,  203 

Occipital  bone,  190,  192 

depression,  142 
Occulomotor,  III,  nerve,  462 
Odontoblasts,  325 
Odontoid  process  (dens),  184 
(Esophageal  region,  317 
(Esophagus,  the,  335 

anomalies  of,  356 
Olfactory  apparatus,  see  Nose 

area  (see  also  Archipallium) ,  558 

bulbs,  452,  541 

lobes,  469,  478,  540,  541 

anterior,  469,  539,  540,  541,  579 
posterior,  469,  539,  540,  54i>  579 

I,  nerve,  467,  468,  501,  5°5 

peduncle,  541 

placodes,  579 

stalk,  541 

tracts,  467,  468,  505,  537 


INDEX 


643 


Olives,  accessory,  520 

inferior,  466,  519,  520,  524 

superior,  523 

Olivo-cerebellar  fibers,  521,  529 
Oraenta,  anomalies  of,  382 
Omental  bursa,  378 

epiploic  foramen  of,  378 
Omentum,  377 

greater,  378 

lesser,  379 
Omosternum,  211 
Omphalocele,  610 
Omphalomesenteric  arteries,  101,  103,  218,  246 

veins,   102,   218 
Oocyte,  primary,  21,  22,  24 

secondary,  22,  24 
Oogonia,  22,  24 
Opercula  of  insula,  552,  553 
Optic  apparatus,  see  Eye 

chiasma,  505,  531 

cup,  566,  469,  577 

depression,  563 

evagination,  564,  576 

lobes,  455,  467,  468 

II,  nerve,  454,  467,  5Q5,  53°,  57$ 

neurone,  first  or  distal,  573 
second  or  middle,  573 

radiation,  470,  471 

stalk,  564,  576 

thalami,  576 

tract,  468,  505,  530,  576 

vesicle  area,  564 

vesicles,  140,  454,  474,  564 
Ora  serrata,  570 
Oral  fossa,  139,  147 

pit,  318 

Orbitosphenoid  bone,  191 
Organ  of  Corti,  460,  467,  558,  587 

of  Giraldes,  417 

of  Rosenmiiller,  415 
Organogenesis,  159 
Os  calcis  (calcaneus),  204 

centrale,  213 

coxae,  203 

Ossa  suprasternalia,  185 
Osseous  tissue,  169 
Ossification  center,  171,  174 

endochondral,  172 

intracartilaginous,  172 

intramembranous,  169 

subperiosteal,  172, 174 

stage,  182 
Osteoblasts,  171,  273 


Osteoclasts,  171, 177,  273 
Osteogenetic  tissue,  171,  173 
Ostium  abdominale  tubae,  414 
Otic  ganglion,  501 
Otocyst,  582 
Ova,  centrolecithal,  44 

classification  of,  12 

meiolecithal,  12 

mesolecithal,  12 

polylecithal,  12 

primitive,  408 
number  of,  410 

telolecithal,  12 
Ovarian  cysts,  602 

(Graafian)  follicle,  409 
liquor  folliculi,  409 
rupture  of,  410 
stratum  granulosum  of,  409 

zona  pellucida,  409 

radiata,  409 

Ovarian  ligament,  the,  422 
Ovary,  the,  10 

anomalies  of,  433 

corpus  hsemorrhagicum,  411 
luteum,  410 

descent  of,  422,  437 

diverticulum  of  Nuck,  422 

egg  nests,  408 

ligaments  of,  422 

medullary  cords  of,  406,  407 

migration  of,  417,  422 

Mullerian  duct  of,  413 

parasitic  growths  of,  601 

Pfliiger's  egg  cords  of,  408 

primary  Graafian  follicle  of,  408 

rete  of,  407 

stratum  greminativum,  407 

theca  folliculi,  409 
Oviduct,  414 

anomalies  of,  433 

fimbriae,  414 

non-stalked  hydatid  of  Morgagni,  414 

ostium  abdominale  tubae  of,  414 
Ovists,  XIII 
Ovium,  10 
Ovulation,  29,  30 
Ovum,  the,  10,  409 

Bryce  and  Teachers,  86,  90,  92 

containing  two  originally  distinct  anlagen, 

599 

faulty  implantation  of,  615 
fertilization  of,  33 
of  human,  37 


644 


INDEX 


Ovum,  fixation  to  uterus,  116 
Graf  Spec's,  86,  154 
Leopold's  85,  154 
maturation  of,  21 
Peters',  86,  154 
size  of,  10 

Palate,  the,  319 

bone,  194 

cleft,  212,  608,  609 

primitive,  580 
Palatine  processes,  319 
Pallium,  455,  467,  474,  538,  539,  541  to  560 

archipallium,  468,  505,  537,  541,  546  to 
552 

association  neurones  of,  468,  528,  530,  558 

calcarine  area  or  region  (see  also    Visual 
area},  557,  558 

corpora  striata,  455, 46^  54* 

cortex  of,  554 

development  of,  468 

hemispheres  of,  457,  470,  474,    538,    541 
to  560 

layer  of  giant  pyramid  cells,  558 

layers  of,  557 

neopallium,  450,  552  to  560 

postcentral  area  of,  471,  555,  557,  558 

precentral  area  of,  472,  557,  558 

rhinencephalon,  455,  467,  540 
Pancreas,  the,  350 

anomalies  of,  358 

cells  of,  354 

connective  tissue  of,  352 

duct  of  Santorini  of,  351,  358 
of  Wirsung  of,  351,  358 

histogenesis  of,  353 

islands  of  Langerhans,  354 
Pander,  XIII 
Papillae,  filiform,  321 

fungiform,  321 

hair,  440 

lingual,  321 

nerve,  438 

renal,  396,  398 

vascular,  438 
Papillares  muscle,  237 
Paradidymis,  the,  414 
Paraphysis,  454,  534 
Paraplasm,  i 
Parasitic  duplicity,  600 

origin  of,  602 

Parasitic  structures  in  the  sexual  glands,  601 
Parathyreoids,  332 


Parietal  bones,  194 

cavity,  227 
of  His,  372 

mesoderm,  71,  83,  134,  370 

recess,  dorsal,  of  His,  372 
Parolfactory  area  of  G.  Elliot  Smith  (see  also 

Preterminal  area),  469,  541 
Paroophoron,  the,  416 
Parovarium,  the,  415 
Pars  basilaris,  190 

ciliaris  retinae,  577 

cystica,  345 

hepatica,  345 

mastoidea,  191 

optica  retinae,  577 

petrosa,  191 

squamosa,  190 

subthalamica,  see  Hypolhalamus 
Partes  laterales,  190 
Patella,  the,  204 
Pathological  embryos,  154 
Paton,  concerning  development  of  pyramids, 

555 

concerning  peripheral  nerves,  494 
Peduncles  of  cerebellum,  middle,  466,  471,  473, 

523,  530 

inferior  cerebellar,  see  Resliform  body 

superior,  466,  471,  473,  530 
Pellicle  of  cytoplasm,  168 
Pelvic  girdle,  203 
Penis,  the,  424 

supernumerary,  601 
Perforated  space,  posterior,  533 
Perforatorium,  14 
Pericardial  cavity,  primitive,  84 
Pericardium,  the,  370,  377 

anomalies  of,  382 
Perichondrium,  173 
Periderm,  the,  437 
Perilymph,  586 
Perilymphatic  space,  586 
Perimysium,  311 
Perineal  body,  the,  424 
Perobrachius,  611 
Perichordal  sheath,  186 
Periosteal  buds,  173 
Periosteum,  171 
Periotic  capsule,  189 
Peripheral      nervous      system,     see     Nervous 

system,  peripheral 
Peristomal  mesoderm,  54,  73 
Peritoneum,  382 
Peritonsillar  fissure,  526 


INDEX 


645 


Perivitelline  space,  n 

Permanent  teeth,  327 

Peromelus,  611 

Peropus,  611 

Persistence  of  the  cloaca,  357 

Pes  pedunculi,  466,  471,  523,  524,  558 

Peter,  concerning  nasal  sac,  579,  580 

concerning  origin  of  endolymphatic  appen- 
dage in  Amphibia,  583 
Peters'  ovum,  86,  in,  135 
Peyer's  patches,  344 
Pfluger's  egg  cords,  408 
Phaeochrome  cells,  426 

granules,  426 
Phaeochromoblasts,  427 
Phalanges,  201 
Pharyngeal  membrane,  318,  330 

region,  317 

tonsils,  330 

Pharyngopalatine  arch,  330 
Pharynx,  the,  329 

anomalies  of,  356 

development  of,  329 

glossopalatine  arch,  330 

pharyngopalatine  arch,  330 

pillars  of  the  fauces,  330 
Physico-chemical  theory  of  monsters,  613 
Piersol,  classification  of  malformations   of  the 

extremities,  610 
Pigment,  438 

of  neurones,  478,  489 
Pillars  of  the  fauces,  330 
Pineal  body,  454,  467,  533 

stalk,  533 
Pisiform,  201 

Pituitary  body,  irregular  tumors  of,  600 
Placenta,  no 

anomalies  of,  130 

annular,  130 

attachment  of,   to  ovum  and  to  uterine 
wall,  128 

bipartita,  130 

blood  vessels  of,  127 

chorion  frondosum,  118,  120 

decidua  basalis,  118,  120 

discoidal,  no 

duplex,  131 

expulsion  of,  130 

fcetalis,  no 

functions  of,  124 

maternal,  no 

membranacea,  130 

praevia,  128 


Placenta,  relations  of,  to  uterine  mucosa,  1 10, 1 20 

size  of,  128 

spuria,  131 

succenturiata,  131 

uterina,  no 

zonular,  no 
Placenta?,  multiple,  no 
Placental  septa,  123 
Placentalia,  no 
Placodes,  452,  495,  505 

auditory,  582 

epibranchial,  452 

olfactory,  579 

suprabranchial,  452 
Plagiocephaly,  212 
Plasmodi-trophoderm,  117,  121,  122 
Plasmosomes,  2 
Plastids,  2 
Pleura,  the,  366,  377 
Pleural  cavities,  373 
Pleuroperitoneal  membranes,  375 
Pleuroperitoneum,  370 
Plexus,  Auerbach's,  491 

chorioideus,  see  Chorioid  plexus 

Meissner's,  491 

vitelline,  217 
Plica  arcuata,  548 

chorioidea  (fold),  547 

encephali  ventralis,  453 

rhombo-mesencephalica,  475 

semilunaris,  579 
Plicae  palmatae,  415 
Polar  bodies,  21,  22,  25 

differentiation,  12 

relation  to  production  of  monsters,  603 

rays,  6 

Polydactyly,  213,  6n 
Polykaryocytes,  177,  273 
Polylecithal  ova,  12 
Polysomatous  monsters,  613 
Polyspermy,  36 
Pons  varolii,  475,  523 
Pontile  nuclei,  466,  519,  523,  530 
Pontine  flexure,  477 
Porencephaly,  605 
Portio  major,  501 

Postbranchial  branches  of  nerves,  464 
Posterior  arcuate  fissure,  548 

colliculi,  see  Posterior  corpora  quadrigemina 

corpora  quadrigemina,  467,  517,  530 
horn  (dorsal  gray  column),  508 
longitudinal    fasciculus,     see    Fasciculus, 
medial  longitudinal 


646 


INDEX 


Posterior  nares,  320 
Prebranchial  branches  of  nerves,  464 
Precervical  sinus,  143,  147 
Preformation  theory,  XIII 
Preformationists,  XIII 
Pregnancy,  abdominal,  30,  38 

mammary  gland,  during,  443 

proof  of,  124 

tubal,  30,  38 
Premolar  teeth,  327 
Premuscle  sheath,  305 

tissue,  296 
Preoptic  recess,  531 
Prepuce,  in  the  female,  424 

in  the  male,  424 
Presphenoid  bone,  191 

Preterminal  area  of  G.  Elliot  Smith,  469,  541 
Primary  areas  or  fields  of  Flechsig,  558 

germ  layers  (see  also  Germ  layers),  51 

oocyte,  21,  22,  24 

spermatocytes,  17,  19,  24 
Primitive  body  cavity  (ccelom),  71 

coordinating  mechanism,  504 

entoderm,  133 

groove,  6 1,  86 

gut  (see  also  Archenteron),  51,  72,  316,  370 

intestinal  cord,  in  the  chick,  62,  77 
in  Mammals,  66 
in  Reptiles,  63 

organs,  52 

pericardial  cavity,  84,  227,  311,  371 

segments,  68,  139,  293,  300 

streak,  in  the  chick,  61 

in  Mammals,  65 
Primordial  cranium,  189 
Proamnion,  80,  104 
Processus  neuroporicus,  454 

reticularis,  511,  516 

vaginalis  peritonei,  420 

Production  of  duplicate  (polysomatous)  mon- 
sters, 613 

of  monsters  in  single  embryos,  614 
Progamous  determination  of  sex,  412 
Projection  fields,  558 
Proliferation  islands,  123 
Pronephric  duct,  384,  385 
Pronephros,  the,  384 

pronephric  duct  of,  384 
tubules  of,  385 

significance  of,  385 
Pronucleus,  female,  23,  33 

male,  23,  33 
Prophase,  4 


Prosencephalon  (fore-brain),  454,  457,  467 

diencephalon,  455,  467 

peripheral  neurones  of,  501 

telencephalon,  455,  467 
Prosopopagus  parasiticus,  600 
Prostate  gland,  402 
Protentoderm,  54 

of  Amphibians,  54,  56 

of  Birds,  60 

of  Mammals,  66 

of  Reptiles,  59 
Protoplasm,  structure  of,  i 
Protozoa,  cell- division  in,  4 

conjugation  in,  38 
Psalterium,  see  Fornix  commissure 
Pterygoid  hamulus,  191 

process,  191,  194 
Pubis,  the,  203 
Pulmonary  artery,  235,  243 
Pulp  of  teeth,  325,  326 
Pulpy  nuclei,  179 
Pulvinar  thalami,  533 
Purkinje  cells,  527,  529 
Pygopagus,  596 

Pyramids  (see  also  Tracts,  pyramidal},  472,  521, 
523,  524 

Quadrigemina,   anterior,  see  Anterior  corpora 

quadrigemina 

posterior,     see    Posterior    corpora     quad- 
rigemina 

Rabbit,  formation  of  amnion  of,  104 
Rabl,  concerning  origin  of  vitreous,  575 

concerning  sex  cells,  404 
Rachischisis,  313,  605,  607 

cystica,  605 
Radius,  200 
Ramus,  196 

communicans,  gray,  492 

white,  487,  492 
Raphe  (of  epichordal  segmental  brain),  515 

(of  scrotum),  426 
Rathke's  pocket,  319 

pouch,  531 
Receptors,  448,  451,  457,  460,  462 

visual,  501,  505 
Recessus  postopticus,  454,  531 

praeopticus,  454,  531 
Recklinghausen,     von,     concerning     deficient 

growth  of  blastoderm,  607 
Rectum,  the,  341,  400 


INDEX 


647 


Red  blood  cells,  270 

Reduction  of  chromosomes  (see  also  Matura- 
tion), 17,  410 
Reflex  arc,  506 

three-neurone,  449 

two-neurone,  448 
Regnier  de  Graaf,  XIII 
Reichert,  XIV 
Rejuvenescence  theory,  38 
Remak,  views  of  cell-division,  4 
Renal  corpuscle,  397 

papillae,  396 

pelvis,  primitive,  391 

pyramids,  397 

tubules,  convoluted,  393 

straight,  391 
Respiratory  system,  the,  360 

anomalies  of,  368 

larynx,  361 

lungs,  364 

trachea,  363 

Restiform  body,  466,  521 
Rete  cords,  404 

ovarii,  407 

testis,  411,  412 
Retention  cysts,  610 

Reticular  formation,  465,  471,  515  to  518 
gray,  516 
white,  516 

tissue,  origin  of  fibers  of,  16 
Retina,  454,  501,  505,  570 

amacrine  cells  of,  572 

area  centralis,  572 

bipolar  cells  of,  505,  573 

cone  bipolars,  574 

defective  pigmentation  of,  445 

differentiation  of  cells  of  nuclear  layer,  572 

distal  (first)  optic  neurone,  573 

fovea  centralis,  572 

layer  of  ganglion  cells  of,  571 
of  nerve  fibers  of,  571 

macula  lutea,  572 

middle  (second)  optic  neurone,  573 

Muller's  or  sustentacular  cells,  572 

nervous  part,  570 

non-nervous  part,  570 

ora  serrata,  570 

pigmented  layer,  570 

primitive  nuclear  layer  of,  571 

rod  and  cone  cells  of,  572,  573 

bipolars,  574 

Retterer,  concerning  lymphatic  tissue  of  ton- 
sils, 330 


Rhinencephalon,  455,  467,  505,  537,  540  to 

54i 
Rhombencephalon  (rhombic  brain),  454,  475, 

495 

Rhombic  brain  (rhombencephalon),  461,  475 
cerebellum,  455 
tela  chorioidea,  455 

grooves,  489 

lip,  513,  519,  525 

Rhombo-mesencephalic  fold,  454,  475 
Rhythmical  contractions,  98,  112 
Ribs,  the,  184 

capitulum  of,  185 

costo-vertebral  ligaments  of,  184 

foramen  trans versarium,  185 

ossification  of,  185 

tuberculum  of,  185 
Rods,  501,  505,  572,  573 
Rolando,  fissure  of,  554 

substantia  gelatinosa  of,  520 

tuberculum  of,  524 

Roof  plate  (dorsal  median  plate),  453,  473,  513 
Root  fibers,  afferent,  451 

sheath,  the,  440 

Rosenberg's  theory  concerning  vertebrae,  210 
Rosenmiiller,  organ  of,  415 
Rotation  of  extremities,  151 
Roux,  concerning  source  of  parasitic  growths, 

604 

Rubro-spinal  tract,  466,  511 
Rupture  of  the  membranes,  113 

Saccule,  586 
Sacral  flexure,  140 
Salivary  glands,  the,  327 

crescents  of  Gianuzzi,  329 

histogenesis  of,  328 

sublingual,  327 

submaxillary,  327 
Santorini,  duct  of,  351 
Sarcoplasm,  309 
Scala  media,  586 

tympani,  586,  587 

vestibuli,  586,  587 

Schaper,  concerning  development  of  cerebel- 
lum, 527 

Scaphocephaly,  212 
Scapula,  199 
Schleiden,  XIV 

Schmidt,  concerning  mammary  gland,  442 
Schultz,  concerning  potentiality  of  germ  cells, 

604 
Schwann,  XIV 


648 


INDEX 


Sclera,  575 

Sclerotome,  163,  179,  293,  307 
Scrotum,  the,  420,  426 
Sebaceous  glands,  the,  442 
Secondary  egg  membranes,  13 

oocyte,  22,  24 
Secretory  function,  329 

Segmental  part  of  epichordal  brain,  457,  459 
Segmentation  (see  also  Cleavage),  40 

cavity,  47 

cells,   development   of   isolated  group  of, 

to  form  monsters,  603 
Segments,  primitive,  68,  139,  293,  300 

of  segmental  brain  and  cord,  505,  506 
Semilunar  ganglion,  460 
Seminal  filament  or  spermatozoon,  10,  13 

vesicles,  416 

Seminiferous  tubules,  411 
Sense  organs,  special,  563 

anomalies  of,  591 

ear,  582 

eye,  563 

nose,  579 
Septa,  the,  233 

anomalies  of,  285 
Septal  marginal  layer,  514 
Septum  aorticum,  235 

atriorum,  233 

medullae,  514 

pellucidum,  469,  552 

spurium,  236 

superius,  233 

trans versum   (see  also  Diaphragm),   372, 
374,  377 

ventriculorum,  235 
Serosa,  103 
Sertoli,  cells  of,  17,  21 
Sex  cells,  404 

cords,  405 

determination  of,  27 
Sexual  elements,  404 
Sheaths,  myelin  (medullary),  478,  494 

neurilemma,  478 

Sherrington,    concerning  effectors  and  recep- 
tors, 448 

Shoulder  girdle,  199 
Siamese  twins,  597 
Sigmoid  colon,  340 

mesocolon,  381 
Sinus,  cavernous,  251 

confluence  of,  252 

coronarius,  254 

frontal,  580 


Sinus,  maxillary,  580 
petrosal,  253 
sagittal,  253 
sphenoidal,  580 
terminalis,  218 
transverse,  252 
venosus,  222,  232 
Sinusoidal  circulation,  347 
Sinusoids,  260,  346,  347 
Situs  viscerum  inversus,  354 
Skeletal  musculature,  see  Musculature,  skeletal 
system,  anomalies  of,  209 
appendicular  skeleton,  198 
axial  skeleton,  178 
development  of  the,  161 

of  joints,  205 
head  skeleton,  186 
notochord,  178 
ribs,  184 
sternum,  185 
vertebrae,  179 

Skeleton,  axail  (see  also  Axial  skeleton),  178 
appendicular,     (see     also     Appendicular 

skeleton),  198 
Skin,  the,  437 

anomalies  of,  4/14 
dermis,  438 
epidermis,  437 
glands  of,  442 
pigment  of,  438 
Skull,  defects  of,  604 

development  of,  186 
Smegma  embryonum,  442 
Smith,  G.  Elliott,  concerning  archipallium,  469 
Smooth  muscle,  311 

histogenesis  of,  312 
Sole  plate,  439 

Somaesthetic  area  of  pallium,  470,  557,  558, 
Somatic  area  (see  also  Pallium,  precentral  area), 

558 

segmentation,  450,  460 
structures,  458 
Somatochrome  cells,  489 
Somatopleure,  71,  105,  370 
Somites,  mesodermic,  68 
Sperm,  10,  17 
Spermatids,  17,  19,  28 
Spermatocytes,  17 
primary,  17,  24 
secondary,  18,  22,  24,  28 
Spermatogenic  cells,  17 
Spermatogenesis,  17 
Spermatogonia,  17,  24 


INDEX 


649 


Spermatozoon,  the,  10,  13,  19 
diagram  of,  14 
discovery  of,  XIII 
flagellate,  13 
Spermium,  10 
Sphenoid  bone,  191,  193 
Sphenomandibular  ligament,  196 
Sphenopagus,  600 
Sphenopalatine  ganglion,  501 
Spigelius,  lobe  of,  349 
Spina  bifida,  605,  606,  607 
cystica,  605 
occulta,  606 

Spinal  accessory,  XI,  nerve,  464,  495 
cord,  the,  453,  454,  473,  506 
Clarke's  column,  466,  511 
dorsal  funiculi,  490,  503,  507 
gray  column,  458,  508 
septum  of,  510 
growth  of,  512 
lack  of,  606 
malformations  of,  605 
ventral  funiculi,  507 
gray  column,  458 
ventro-lateral  funiculus,  507 
ganglion,  490,  491 

cells,  unipolarization  of,  491 
meningocele,  606 
V,  460,  501,  518 
Spindle,  achromatic,  4 

central,  4 

Spino-cerebellar  tracts,  466,  471,  512 
Spiral  fibers  of  spermatozoon,  14 
filament,  20 
lamina,  587 
Spireme,  closed,  5 
open,  5 
thread,  5 

segmentation  of,  18 
Splanchnic  mesoderm,  102,  341 
or  visceral  structures,  458 
Splanchnoccel,  71 
Splanchnopleure,  71,  105,  370 
Spleen,  the,  283 

cavernous  veins  of,  284 
cells,  285 

haematopoietic  function  of,  284 
pulp  cords  of,  284 
splenic  corpuscles  of,  284 
Splenic  corpuscles,  284 
Spongioblasts,  479,  483 
Spongioplasm,  i 
Spongy  bone,  171 


Stapes,  197,  589 
Sternopagus,  597 
Sternum,  the,  185 

corpus  sterni,  186 

cleft,  211 

malformations  of,  597 

manubrium  sterni,  186 

ossification  of,  186 

xyphoid  process  of,  186 
St.  Hilaire,  concerning  malformations, 
Stockard,  on  production  of  monsters,  614 
Stomach,  the,  335 

anomalies  of,  357 

practical  suggestions  for  study  of,  358 

region,  317 

rotation  of,  336 

Strahl,  concerning  the  mammary  gland,  442 
Stratum  granulosum,  409 

cells  of,  410 
Streeter,  concerning  the  acoustic  nerve,  589 

concerning  atrium  of  inner  ear,  583 

concerning  development    of  IX,    X,   XI, 
cranial  nerves,  495,  496 

concerning  floor  of  fourth  ventricle,  524 

concerning   origin   of   endolymphatic   ap- 
pendage in  man,  583 

concerning  origin  of  genu  facialis,    715 

concerning  rhombic  grooves,  489 
Stria  medullaris,  533,  538 

semicircularis,  543 

terminalis,  543,  548 
Striae  Lancisi,  551 
Striated  involuntary  muscle  tissue,  311 

voluntary  muscle  tissue,  cells  of,  307 
endomysium  of,  311 
epimysium  of,  311 
fibers  of,  308 
histogenesis  of,  307 
intermuscular  tissue  of,  311 
perimysium  of,  311 
sarcoplasm,  309 
Stylohyoid  ligament,  197 
Styloid  process,  192,  197 
Subclavian  artery,  242,  244,  248 
Sublingual  gland,  328 
Submaxillary  ganglion,  501 

gland,  327 

Subperiosteal  ossification,  172,  174 
Substantia  gelatinosa  of  Rolando,  520 

propria  corneae,  578 
Sudoriferous  glands,  the,  442 
Sulcus  hypothalamicus,  531 

limitans,  477,  512,  524 


650 


INDEX 


Sulcus,  longitudinalis,  235 

Monroi,  531 
Superior  peduncle  of  cerebellum,  466,  471,  473, 

530 

Supplemental  cleavage,  60 
Supracondyloid  process,  212 
Supraglenoidal  tuberosity,  199 
Supraoccipital  bone,  190 
Suprarenal  glands,  426 
chromaffin  cells,  426 
cortical  substance  of,  427 
lipoid  granules  of,  426 
medullary  substance  of,  427 
organs,  428 

phaeochrome  cells  of,  426 
relation  to  kidney,  428 

Suprasegmental  structures  of  Adolf  Meyer  (see 
also  Cerebellum,  Mid-brain  roof,  Cor- 
pora quadrigemina  and  Pallium),  450, 
457,  466,  467,  505,  506 
characteristics  of,  457 
connections  of,  see  Cerebellum,  Mid-brain 
roof,    Corpora    quadrigemina,    Archi- 
pallium  and  Neopallium 
tracts  to  (see  also  Cerebellum,  Mid-brain 
roof,   Corpora    quadrigemina,    Archi- 
pallium  and   Neopallium),  466,   471, 

5ii 

Suprasternal  bones,  185,  211 
Sylvii,  fossa  of,  539,  540,  552 
Symblepharon,  608 
Symmetrical  duplicity,  594 

anterior  union,  598 

complete  duplicity,  593,  594 

middle  union,  597 

multiplicity,  599 

origin  of,  599 

posterior  union,  596 
Sympathetic  (autonomic)  system,  458 

nervous     system,     see     Nervous     system, 

sympathetic 
Sympathoblasts,  427 
Symphysis  of  lower  jaws,  318 
Sympus  apus,  611 

dipus,  611 

monopus,  611 

symelus  siren,  611 
Synapta,  cleavage  in,  41 
Synarthrosis,  206 
Syncephalus,  598 
Synchondrosis,  206 
Syncytial  layer,  121 
Syncytium  of  heart  muscle,  312 


Syndesmosis,  206 
Synophthalmia,  608 
Synosteosis,  211 
Synotia,  591,  598 
Synotus,  608,  609 
Synovial  fluid,  207 
Syringomyelocele,  606 

Tactile  corpuscles  of  Meissner,  438 
Taenia  fimbrias,  548 

of  cerebellum,  525 

of  cerebral  hemispheres,  542 

of  medulla,  513 

Tail,  gradual  shortening  of,  140,  144,  145 
Talus,  204 

Tarsus,  bones  of  the,  204 
Taste  buds  (see  also  Gustatory  system),  450,  460 
Tautomeric  column  cells,  503 
Teeth,  the,  322 

dental  groove,  323 
papilla,  323 
shelf,  323 

dentinal  canals,  326 
fibers  of,  326 
pulp  of,  325 

dentine,  323,  325,  326 

enamel,  324 
organ,  323 

membrana  preformativa,  325 

milk,  323 

odontoblasts,  325 

permanent,  326 

true  molars,  326 
Tegmental  swelling,  517,  535 
Tegmentum,  524,  538 
Tela  chorioidea,  455,  533 
Telencephalon  (end-brain),  84,  455,  467,  538  to 
56i 

corpus  striatum,  455,  467,  474,  478,  539 

pallium,  455,  467,  474,  538,  539 

rhinencephalon,  455,  467,  505,  537,  540  to 

54i 

Telolecithal  eggs  (ova),  12 
Telophase,  6 
Temporal  bone,  191,  193 

lobe,  542 
Tendons,  167 
Teratogenesis,  593 

causes  underlying  origin  of  monsters,  612 
malformations  involving   more   than   one 

individual,  593 

malformations   involving   one   individual, 
604 


INDEX 


651 


Teratoid  tumors,  429,  430 

Teratomata,  604 

Terminal  arborizations,  487,  504 

areas  of  Flechsig,  559 
Testicle,  the,  411 

anomalies  of,  432 

cells  of,  412 

descent  of,  419,  437 

mediastinum  testis,  412 

migration  of,  418,  422 

processus  vaginalis  peritonei,  420 

rete  testis,  411,  412 

seminiferous  tubules,  convoluted,  411 
straight,  411 

stroma  of,  412 

tunica  albuginea  of,  405,  411 

vaginalis  propria,  422 
Testis,  mediastinum,  412 

parasitic  growths  of,  602 

rete,  411,  412 
Tetrabrachius,  597 
Tetrads,  18,  22 

origin  of,  18 
Thalamic  radiations,  470,  471,  537,  545,  546, 

554 

Thalamus,  467,  478,  505,  536,  546 
Theca  folliculi,  409 
Theoria  generationis,  XIII 
Thigh,_development  of,  150 
Thoracic  duct,  275,  279 

region,  defects  of,  610 
Thoracogastroschisis,  610 
Thoracopagus,  597 

parasiticus,  597 
Thoracoschisis,  382 
Thymus  gland,  285,  333 

anomalies  of,  456 

atrophy  of,  334 

histogenesis  of,  334 

malformations  of,  597 

tumors  of,  601 

Thyng,  concerning  anomalies  of  pancreas,  358 
Thyreoglossal  duct,  332 
Thyreoid  gland,  331 

anomalies  of,  356 

colloid  secretion  of,  331 

epithelial  bodies,  332 

its  relation  to  formation  of  blood  cells,  335 

parathyreoids,  332 

thyreoglossal  duct  of,  332 
Thyreoids,  lateral,  332 

theories  concerning,  332 
Tibia,  204 


Tissues,  adenoid,  331 

adipose,  167 

chromamn,  429 

connective,  161 

lymphatic,  of  the  tongue,  330 

mesenchymal,  165 

muscle,  307,  311 

nephrogenic,  392 

osseous,  169 

premuscle,  296 

retroperitoneal,  429 

subcutaneous,  438 
Toes,  development  of,  150 
Tongue,  the,  320 

filiform  papillae  of,  321 

foramen  caecum  liguae,  321 

fungiform  papillae  of,  321 

inner vation  of,  462 

lingual  papillae  of,  321 

lingualis  muscle  of,  321 

tuberculum  impar,  320 

vallate  papillae  of,  322 
Tonsilla,  526 
Tonsils,  the,  330 

crypts  of,  330 

lingual,  330 

lymph  follicles  of,  330 

pharyngeal,  330 

Tooth  tumors,  developmental,  327 
Torneux,  concerning  malformations  of  neural 

tube,  607 
Tornier,  concerning  production  of  vertebrate 

monsters,  613 
Trabeculae  carneae,  237 
Trachea,  the,  363 
Tracts,  see  also  Fascicttli, 

central  tegmental,  519 

cortico-spinal,  see  Tracts,  pyramidal 

Flechsig's,  466,  471,  512,  521 

from  Deiter's  nucleus,  466,  511 

from  suprasegmental  structures,  471,  512 

Gower's,  466,  471,  512,  521 

gustatory  (see  also  Tractus  solitarius) ,  462, 
467,  468 

olfactory,  467,  468,  505,  537 

optic,  467,  468,  505,  577 

predorsal,  467,  530 

pyramidal,  471,  472,  512,  521,  526,  524, 
558 

reticular      formation     +     ventro- lateral 
ground  bundle  system,  504 

reticulo-spinal,  516 

rubro-spinal,  466,  511,  517 


652 


INDEX 


Tracts,  secondary  and  tertiary  olfactory,  505 
optic  (see  also  Optic  nerve),  505 

spino-cerebellar  (dorsal),  466,  471,  512,  521 
(ventral),  466,  472,  512,  521 

spino-tectal  and  thalamic,  471,  512 

to  Deiter's  nucleus,  466 

to   suprasegmental   structures,    466,    471, 

511,  518  to  525 

Tractus  solitarius  (communis)  of  VII,  IX  and 
X  nerves,  462,  499,  503,  504,  518, 
521 

Tragus,  594 

Transposition  of  the  viscera,  354 
Transverse  mesocolon,  380 
Trapezium  (bone),  201 

(of  medulla),  523 
Trapezoid,  the,  201 

area  of  His   (see  also  Preterminal  area), 

469,  54i 

Tribrachius,  597 
Tricephalus,  599 
Trigeminus,  V,  nerve,  460,  462,  464 

Gasserian  ganglion,  460 

spinal  V  root,  460 
Trigonum  (bone),  213 

(brain),  541 
Triquetral  bone,  200 
Trochanters,  204 
Trochlea,  200 
Trochlear,  IV,  nerve,  462 
Trophoderm,  48,  63,  133 
Truncus  arteriosus,  219 
Tsuda,  concerning  production  of  spina  bifida, 

614 

Tubal  pregnancy,  30,  38 
Tuber  cinereum,  533 
Tubercles,  greater,  200 

lesser,  200 
Tuberculum  of  rib,  185 

impar,  320 

of  Rolando,  524 
Tubular  form  of  blastoderm,  in  chick,  81 

in  Mammals,  85 

Tumors  of  sexual  glands,  origin  of,  603 
Tunica  albuginea,  405 

vasculosa  lends,  569 

dartos,  438 

vaginalis  propria,  422 
Turbinated  bones,  192 
Twins,  equal  monochorionic,  593,  594,  595 

free  duplicities,  593 

unequal  monochorionic,  594 
Tympanum,  590 


Ulna,  200 

Umbilical  arteries,  103,  222,  241 
coelom,  338 
cord,  128,  138 
anomalies  of,  131 
in  Mammals,  107,  138 
in  man,  128 
length  of,  human,  130 
hernia,  113,  622 
ligament,  middle,  115,  401 
veins,  103,  222,  250 
Umbilicus,  dermal,  101 
double,  596 
intestinal,  101 
Unicornuate  uterus,  433 
Unilateral  hermaphroditism,  434 
Unipolarization  of  spinal  ganglion  cells,  491 
Unna,  concerning  anomalies  of  hair,  445 
Uracho-vesical  fistula,  432 
Urachus,  102,  115,  401 
anomalies  of,  431 
Urdarmstrang,  66 
Ureters,  the,  391 

anomalies  of,  430 
relations  of,  to  cardinal  veins,  260 
Urethra,  the,  401,  424 
anomalies  of,  432 
Urinary  bladder,  the,  400,  401 
"Urinary  fistula,"  115 
Urogenital  sinus,  the,  400 
system,  the,  384 
anomalies  of,  429 

development  of  suprarenal  glands,  426 
genital  glands,  403 
kidney,  391 
mesonephros,  386 
metanephros,  391 
pronephros,  384 
urethra,  400 
urinary  bladder,  400 
urogenital  sinus,  400 
Urorectal  fold,  the,  400 
Uterus,  the,  415 

anomalies  of,  433 
bicornuate,  433 
bipartite,  433 
didelphys,  433 
fixation  of  ovum  to,  116 
infantile,  433 
masculinus,  417 
relation  of  placenta  to,  in 
unicornuate,  433 
Utricle,  586 


INDEX 


653 


Utriculosaccular  duct,  586 
Utriculus  prostaticus,  417 
Uvula,  526 

Vacuole,  2 
Vagina,  the,  415 

anomalies  of,  433 
Vagus,  X,  nerve,  462,  464 
Valves,  the,  236 

anomalies  of,  285 
Valvula  bicuspidalis,  237 

mitralis,  237 

sinus  coronarii,  236 

tricuspidalis,  237 

venae  cavae  inferioris,  236 
Valvulae  semilunares  aortae,  237 

semilunares  arteriae  pulmonalis,  237 

venosae,  236 
Vas  deferens,  416 

epididymis,  423 
Vasa  aberrantia,  349,  423 

efferentia,  416 
Vascular  arteries,  240 

blood  vessels,  216 

blood  and  blood  cells,  267 

changes  in  the  circulation  at  birth,  265 

development  of  the,  216 

heart,  227 

histogenesis  of  blood  cells,  267 

lymphatic  system,  273 

system,  anomalies  of,  285,  595 

veins,  250 

Vasculogenesis,  principles  of,  224 
Vegetative  pole  (macromere),  52 
Veins,  accessory  hemiarzygos,  260 

anomalies  of,  288,  607 

ascending  lumbar,  260 

axillary,  263 

azygos,  259 

basilic,  263 

brachial,  263 

cardinal,  251,  253,  255 

cavernous,  282 

cephalic,  262 

cerebral,  251 

common  iliac,  259 

femoral,  265 

fibular,  264 

hemiazygos,  260 

hepatic,  262 

inferior  sagittal,  253 

internal  spermatic,  258 

jugular,  254 


Veins,  jugulocephalic,  264 

lateralis  capitis,  251 

of  Galen,  253 

omphalomesenteric,  102,  218,  250 

ovarian,  258 

portal,  261 

primary  ulnar,  262 

radial,  263 

renal,  257 

revehent,  256 

saphenous,  265 

sciatic,  265 

subcardinal,  256 

subclavian,  254,  266 

subintestinal,  71 

supracardinal,  259 

suprarenal,  259 

testicular,  258 

tibial,  264,  265 

umbilical,  103,  222,  250 

vitelline,  102,  218 
Velum,  anterior  medullary,  526 

posterior  medullary,  513,  526 

transversum,  454,  534 
Vena  cava,  inferior,  255,  257 

superior,  254 
Veno-lymphatics,  280 
Ventral  cephalic  fold  of  brain,  453 

mesentery,  377 

mesogastrium,  377 

root  fibers,  see  Efferent  root  fibers 
Ventricle,  361 

of  Verga,  552 
Ventricles  of  the  brain,  456 

fourth,  456,  478- 

lateral,  456,  542 

anterior  horn  of,  542  ^* 
descending  horn  of,  542""" 
posterior  horn  of,  542 

third,  456,  478 
Ventricular  septum,  233 
Ventro-lateral  plate,  see  Basal  plate 
Vermiform  appendix,  341 
Vermis,  526 

Vernix  caseosa,  437,  442 
Vertebrae,  the,  179 

alternation  of  vertebrae  and  myotomes, 

anomalies  of,  209 

blastemal  stage  of,  180 

bodies  of,  180 

cartilaginous  stage  of,  180 

costal  process,  180 

intervertebral  fibrocartilage,  180 


654 


INDEX 


Vertebrae,  ligaments  of,  184 

ossification  stage,  182 

sclerotomes  of,  178 
Vertebrae  cervical,  defects  of,  604 
Vertebral  arch,  180 

articular  process  of,  182 

spinous  process  of,  182 

transverse  process  of,  182 
Vertebrate,  the  definition  of,  450 

differentiation  of  the  anterior  end  of,  450 

nervous  system,  see  Nervous  system,  ver- 
tebrate 

Vesical  fissure,  432 
Vesicle,  auditory,  582 

blastodermic,  134 

optic,  140,  564 
Vesicles,  brain,  454,  473 

seminal,  416 
Vestibular  ganglion  cells,  589 

membrane  (of  Reissner),  587 

nerve,  589 

part  of  acoustic  (auditory)  nerve,  462 
descending  root  of,  462 

pouch,  583 
Vestibule,  460 
Vestibulum  vaginae,  424 
Vicq  d'Azyr's  bundle,  537 
Vignal,  concerning  the  myelin  sheath,  494 
Villi,  chorionic,  no,  118 

fastening,  123 

floating,  123 
Visceral  mesoderm,  71,  83 

musculature,  see  Musculature,  visceral 

neurones,  sympathetic,  451 

or  splanchnic  structures,  458 
Visual  area  of  pallium,  470,  557,  558 

cortex,  557 
Vitelline  arteries,  101,  241 

circulation,  220 

duct,  113 

membrane,  n 

plexus,  217 

veins,  102,  218 
Vitellus,  n 
Vitreous,  575 

humor,  575 
Voral  cords,  superior,  or  false,  361 

true,  361 

Volar  arch,  superficial,  248 
Voluntary  muscle,  striated,  histogenesis  of,  307 

origin  of,  293,  294 
Vomer,  192,  194 
Von  Baer,  XIII 


Von  Baer,  concerning  cell  differentiation,  51 

Von  Baer's  law,  384 

Von  Loewenhoek,  concerning  the  discovery  of 

the  spermatozoon,  XIII 
Von  Spec's  embryo,  86,  136 

Waldeyer,  concerning  site  of  fertilization,  38 

"  Waters,"  the,  113 

Webs  between  digits,  151 

Weismann,  concerning  fertilization,  38 

Wharton's  jelly,  129 

Wheeler,  diagram  showing  amitosis,  4 

White  columns  (see  also  Dorsal  funiculus),  503 

matter  of  cerebral  hemispheres,  554 
of  cord  and  segmental  brain,  504 

ramus  communicans,  487,  492 
Wiedersheim,  concerning  the  mammary  gland, 

443 
concerning  duplicity  with  double  gastru- 

lation,  600 
concerning    the    fertilization    of    eggs    of 

sea-urchin,  34 
Wilson,  J.  F.,  concerning  intermediate  region 

in  the  cord,  524 

concerning  intermediate  plate,  524 
Winslow,  foramen  of,  378 
Wirsung,  duct  of,  351 

Wlassak,  concerning  the  myelin  sheath,  494 
Wolffian  duct,  386 

ridge,  388 
"Wolf's  snout,"  212 

theory  of  epigenesis,  XIII 
Woods,  concerning  sex  cells,  404 
Wyder,  concerning  site  of  fertilization,  38 

X-chromosome,  28 
Xiphoid  process,  186 

malformations  of,  597 
Xiphopagus,  597 

Y-chromosome,  29 

Yolk,  comparison  of  amount  of  in  forms  of 

gastrulation,  57,  64 
entoderm,  in  Amphibians,  54 
in  Birds,  60 
in  Mammals,  66,  68,  81 
granules,  12 

lack  of,  in  Mammals,  104 
plug,  54 
sac,  99,  135 

formation  of  in  chick,  99 
function  of,  100 
in  Mammals,  104,  106 
in  man,  87,  113 


INDEX 


655 


Yolk  sac,  roof  of,  in  chick,  80,  8 1 
in  Mammals,  85 
in  man,  87 
stalk,  loo,  107,  137,  317 

Zander,  concerning  the  nails,  439 
Ziegler,   concerning   malformations   of   neural 
tube,  607 


Ziegler's  fusion  theory  of  symmetrical  duplic- 
ity, 599 
Zona  pellucida,  n,  34,  409 

radiata,  409 
Zonula  Zinnii,  578 
Zonular  placenta,  no 
Zygomatic  bone,  194 
Zymogen  granules,  354 


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